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From Beneath the Skin to the Airway Wall: Understanding the Pathological Role of Adipose Tissue in Comorbid Asthma‐Obesity

Carolyn J. Wang, Peter B. Noble, John G. Elliot, Alan L. James, Kimberley C. W. Wang

10.1002/cphy.c220011

Source: Volume 13, Issue 1, January 2023

Published online: January 2023

Full Article on Wiley Online Library



Abstract

This article provides a contemporary report on the role of adipose tissue in respiratory dysfunction. Adipose tissue is distributed throughout the body, accumulating beneath the skin (subcutaneous), around organs (visceral), and importantly in the context of respiratory disease, has recently been shown to accumulate within the airway wall: “airway‐associated adipose tissue.” Excessive adipose tissue deposition compromises respiratory function and increases the severity of diseases such as asthma. The mechanisms of respiratory impairment are inflammatory, structural, and mechanical in nature, vary depending on the anatomical site of deposition and adipose tissue subtype, and likely contribute to different phenotypes of comorbid asthma‐obesity. An understanding of adipose tissue‐driven pathophysiology provides an opportunity for diagnostic advancement and patient‐specific treatment. As an exemplar, the potential impact of airway‐associated adipose tissue is highlighted, and how this may change the management of a patient with asthma who is also obese. © 2023 American Physiological Society. Compr Physiol 13:4321‐4353, 2023.

Figure 1. Figure 1. Transference of parental obesity to offspring may increase risk of asthma. Maternal and paternal obesity are both associated with increased prevalence of childhood obesity and asthma, which contribute to an intergenerational effect and thus perpetuate the obese‐asthmatic phenotype.
Figure 2. Figure 2. The process of adipogenesis and the mechanism of lipid transport from dietary fat and de novo lipogenesis. On the left, multipotent adipose‐derived stem cells commit to a preadipocytic lineage upon stimulation from BMP4‐activated ZFP423. Preadipocytes undergo proliferation by mitotic clonal expansion in the presence of growth factors such as C/EBPβ and are stimulated by adipogenic factors to terminally differentiate into mature adipocytes, which absorb lipids to form a single lipid droplet (yellow) within the cell cytoplasm. In obesity, grossly hypertrophic adipocytes become apoptotic (red markers) which will initiate an immune response within adipose tissue, resulting in adipose tissue expansion and dysfunction before dying. Saturated adipocytes in obese individuals lead to lipid overspill, which are transported back into the circulation, subsequently increasing serum lipid levels. On the right, exogenous fats are emulsified to liberate TG, which are packaged into transport lipoproteins containing Ch. Lipoproteins circulate lipids in the bloodstream and can be hydrolyzed by LPL to be taken up by target organs such as the liver, lungs, or heart. Carbohydrates are metabolized to form glucose, which are converted to acetyl‐CoA during the process of glycolysis. Fatty acid synthase converts acetyl‐CoA to free fatty acids, which are esterified by DGAT to form TG and are further bundled with Ch into lipoproteins for circulatory transport. Acetyl‐CoA, acetyl coenzyme A; BMP4, bone morphogenetic protein 4; C/EBPα, CCAAT‐enhancer‐binding‐protein alpha; C/EBPβ, CCAAT‐enhancer‐binding‐protein beta; C/EBPδ, CCAAT‐enhancer‐binding‐protein delta; C/EBPγ, CCAAT‐enhancer‐binding‐protein gamma; Ch, cholesterol; DGAT, diglyceride acyltransferase; FABP4, fatty acid‐binding protein 4; GLUT4, glucose transporter type 4; LPL, lipoprotein lipase; PPARγ, proliferator‐activated receptor gamma; SREBP1, sterol regulatory element‐binding protein‐1; TG, triglyceride, ZFP423, zinc finger protein 423.
Figure 3. Figure 3. Autocrine, endocrine, and paracrine signaling of adipose tissue. Adipocytes and SVF cells produce adipokines (red), which act locally in an autocrine manner to disrupt adipose tissue function. Adipokines are secreted into the bloodstream and circulated throughout the body and taken up by other tissues including the pancreas, that is, endocrine signaling. Lipids are deposited in nonadipose tissues such as the liver and the airways, leading to the formation of ectopic adipose tissue. Adipokine release from ectopic adipose tissue deposits affecting nearby tissue (paracrine signaling), as depicted by the dispersion of adipose tissue within the liver. The effects of airway‐associated adipose tissue on the airways are currently unknown. ECM, extracellular matrix; SVF, stromal vascular fraction.
Figure 4. Figure 4. The presence of airway‐associated adipose tissue in the outer airway wall of human tissue at 200× magnification. Airway‐associated adipose tissue is within close proximity to ASM and resides between mucus glands and the adventitia. ASM, airway smooth muscle. Reused, with permission, from Elliot JG, et al., 2019 94.
Figure 5. Figure 5. Airway‐associated adipose tissue is positively correlated with BMI (A) and airway wall area (B). Blue circles and line, Control; red circles and line, Asthmatic. BMI, body mass index; Pbm, basement membrane perimeter. Reused, with permission, from Elliot JG, et al., 2019 94.
Figure 6. Figure 6. Four hypothesized roles of airway‐associated adipose tissue in comorbid asthma‐obesity. (A) Airway inflammation—adipokines (red stars) released from airway‐associated adipose tissue recruit immune cells (neutrophils) to augment airway inflammation; (B) ASM remodeling—the above simulates ASM growth and remodeling; (C) parenchymal uncoupling—airway‐associated adipose tissue in the outer airway wall (and external) prevents transmission of dilatory parenchymal forces; (D) compression—excessive adipose tissue deposition causes an inwardly directed encroachment on the airway lumen. ASM, airway smooth muscle.


Figure 1. Transference of parental obesity to offspring may increase risk of asthma. Maternal and paternal obesity are both associated with increased prevalence of childhood obesity and asthma, which contribute to an intergenerational effect and thus perpetuate the obese‐asthmatic phenotype.


Figure 2. The process of adipogenesis and the mechanism of lipid transport from dietary fat and de novo lipogenesis. On the left, multipotent adipose‐derived stem cells commit to a preadipocytic lineage upon stimulation from BMP4‐activated ZFP423. Preadipocytes undergo proliferation by mitotic clonal expansion in the presence of growth factors such as C/EBPβ and are stimulated by adipogenic factors to terminally differentiate into mature adipocytes, which absorb lipids to form a single lipid droplet (yellow) within the cell cytoplasm. In obesity, grossly hypertrophic adipocytes become apoptotic (red markers) which will initiate an immune response within adipose tissue, resulting in adipose tissue expansion and dysfunction before dying. Saturated adipocytes in obese individuals lead to lipid overspill, which are transported back into the circulation, subsequently increasing serum lipid levels. On the right, exogenous fats are emulsified to liberate TG, which are packaged into transport lipoproteins containing Ch. Lipoproteins circulate lipids in the bloodstream and can be hydrolyzed by LPL to be taken up by target organs such as the liver, lungs, or heart. Carbohydrates are metabolized to form glucose, which are converted to acetyl‐CoA during the process of glycolysis. Fatty acid synthase converts acetyl‐CoA to free fatty acids, which are esterified by DGAT to form TG and are further bundled with Ch into lipoproteins for circulatory transport. Acetyl‐CoA, acetyl coenzyme A; BMP4, bone morphogenetic protein 4; C/EBPα, CCAAT‐enhancer‐binding‐protein alpha; C/EBPβ, CCAAT‐enhancer‐binding‐protein beta; C/EBPδ, CCAAT‐enhancer‐binding‐protein delta; C/EBPγ, CCAAT‐enhancer‐binding‐protein gamma; Ch, cholesterol; DGAT, diglyceride acyltransferase; FABP4, fatty acid‐binding protein 4; GLUT4, glucose transporter type 4; LPL, lipoprotein lipase; PPARγ, proliferator‐activated receptor gamma; SREBP1, sterol regulatory element‐binding protein‐1; TG, triglyceride, ZFP423, zinc finger protein 423.


Figure 3. Autocrine, endocrine, and paracrine signaling of adipose tissue. Adipocytes and SVF cells produce adipokines (red), which act locally in an autocrine manner to disrupt adipose tissue function. Adipokines are secreted into the bloodstream and circulated throughout the body and taken up by other tissues including the pancreas, that is, endocrine signaling. Lipids are deposited in nonadipose tissues such as the liver and the airways, leading to the formation of ectopic adipose tissue. Adipokine release from ectopic adipose tissue deposits affecting nearby tissue (paracrine signaling), as depicted by the dispersion of adipose tissue within the liver. The effects of airway‐associated adipose tissue on the airways are currently unknown. ECM, extracellular matrix; SVF, stromal vascular fraction.


Figure 4. The presence of airway‐associated adipose tissue in the outer airway wall of human tissue at 200× magnification. Airway‐associated adipose tissue is within close proximity to ASM and resides between mucus glands and the adventitia. ASM, airway smooth muscle. Reused, with permission, from Elliot JG, et al., 2019 94.


Figure 5. Airway‐associated adipose tissue is positively correlated with BMI (A) and airway wall area (B). Blue circles and line, Control; red circles and line, Asthmatic. BMI, body mass index; Pbm, basement membrane perimeter. Reused, with permission, from Elliot JG, et al., 2019 94.


Figure 6. Four hypothesized roles of airway‐associated adipose tissue in comorbid asthma‐obesity. (A) Airway inflammation—adipokines (red stars) released from airway‐associated adipose tissue recruit immune cells (neutrophils) to augment airway inflammation; (B) ASM remodeling—the above simulates ASM growth and remodeling; (C) parenchymal uncoupling—airway‐associated adipose tissue in the outer airway wall (and external) prevents transmission of dilatory parenchymal forces; (D) compression—excessive adipose tissue deposition causes an inwardly directed encroachment on the airway lumen. ASM, airway smooth muscle.
References
 1.Aarsland A, Chinkes D, Wolfe RR. Hepatic and whole‐body fat synthesis in humans during carbohydrate overfeeding. Am J Clin Nutr 65: 1774‐1782, 1997.
 2.Achari AE, Jain SK. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int J Mol Sci 18: 1321, 2017.
 3.Adams DC, Hariri LP, Miller AJ, Wang Y, Cho JL, Villiger M, Holz JA, Szabari MV, Hamilos DL, Scott Harris R, Griffith JW, Bouma BE, Luster AD, Medoff BD, Suter MJ. Birefringence microscopy platform for assessing airway smooth muscle structure and function in vivo. Sci Transl Med 8: 359ra131, 2016.
 4.Aikawa T, Shimura S, Sasaki H, Ebina M, Takishima T. Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack. Chest 101: 916‐921, 1992.
 5.Akerman MJ, Calacanis CM, Madsen MK. Relationship between asthma severity and obesity. J Asthma 41: 521‐526, 2004.
 6.Al‐Alwan A, Bates JH, Chapman DG, Kaminsky DA, DeSarno MJ, Irvin CG, Dixon AE. The nonallergic asthma of obesity. A matter of distal lung compliance. Am J Respir Crit Care Med 189: 1494‐1502, 2014.
 7.Al‐Alwan LA, Chang Y, Mogas A, Halayko AJ, Baglole CJ, Martin JG, Rousseau S, Eidelman DH, Hamid Q. Differential roles of CXCL2 and CXCL3 and their receptors in regulating normal and asthmatic airway smooth muscle cell migration. J Immunol 191: 2731‐2741, 2013.
 8.Ali FR. Does this patient have atopic asthma? Clin Med (Lond) 11: 376‐380, 2011.
 9.Alkhouli N, Mansfield J, Green E, Bell J, Knight B, Liversedge N, Tham JC, Welbourn R, Shore AC, Kos K, Winlove CP. The mechanical properties of human adipose tissues and their relationships to the structure and composition of the extracellular matrix. Am J Physiol Endocrinol Metab 305: E1427‐E1435, 2013.
 10.Alkhouri N, Gornicka A, Berk MP, Thapaliya S, Dixon LJ, Kashyap S, Schauer PR, Feldstein AE. Adipocyte apoptosis, a link between obesity, insulin resistance, and hepatic steatosis. J Biol Chem 285: 3428‐3438, 2010.
 11.Alligier M, Meugnier E, Debard C, Lambert‐Porcheron S, Chanseaume E, Sothier M, Loizon E, Hssain AA, Brozek J, Scoazec JY, Morio B, Vidal H, Laville M. Subcutaneous adipose tissue remodeling during the initial phase of weight gain induced by overfeeding in humans. J Clin Endocrinol Metab 97: E183‐E192, 2012.
 12.Al‐Shawwa B, Al‐Huniti N, Titus G, Abu‐Hasan M. Hypercholesterolemia is a potential risk factor for asthma. J Asthma 43: 231‐233, 2006.
 13.Amrani Y, Chen H, Panettieri RA Jr. Activation of tumor necrosis factor receptor 1 in airway smooth muscle: A potential pathway that modulates bronchial hyper‐responsiveness in asthma? Respir Res 1: 49‐53, 2000.
 14.Arner P, Bernard S, Appelsved L, Fu KY, Andersson DP, Salehpour M, Thorell A, Ryden M, Spalding KL. Adipose lipid turnover and long‐term changes in body weight. Nat Med 25: 1385‐1389, 2019.
 15.Ather JL, Van Der Vliet KE, Mank MM, Reed LF, Dixon AE, Poynter ME. Obese adipose tissue modulates proinflammatory responses of mouse airway epithelial cells. Am J Physiol Regul Integr Comp Physiol 321: R79‐R90, 2021.
 16.Australian Institute of Health Welfare. Overweight and Obesity: An Interactive Insight. Canberra: AIHW, 2020. https://www.aihw.gov.au/reports/overweight‐obesity/overweight‐and‐obesity‐an‐interactive‐insight/contents/what‐is‐overweight‐and‐obesity.
 17.Australian Institute of Health Welfare. Asthma. Canberra: AIHW, 2020. https://www.aihw.gov.au/reports/chronic‐respiratory‐conditions/asthma/contents/asthma.
 18.Australian Institute of Health Welfare. Australia's Mothers and Babies Data Visualisations. Canberra: AIHW, 2020. https://www.aihw.gov.au/reports/mothers‐babies/australias‐mothers‐babies/contents/antenatal‐period/body‐mass‐index.
 19.Baack ML, Forred BJ, Larsen TD, Jensen DN, Wachal AL, Khan MA, Vitiello PF. Consequences of a maternal high‐fat diet and late gestation diabetes on the developing rat lung. PLoS One 11: e0160818, 2016.
 20.Babb TG, Wyrick BL, Chase PJ, DeLorey DS, Rodder SG, Feng MY, Ranasinghe KG. Weight loss via diet and exercise improves exercise breathing mechanics in obese men. Chest 140: 454‐460, 2011.
 21.Baek HS, Kim YD, Shin JH, Kim JH, Oh JW, Lee HB. Serum leptin and adiponectin levels correlate with exercise‐induced bronchoconstriction in children with asthma. Ann Allergy Asthma Immunol 107: 14‐21, 2011.
 22.Baffi CW, Winnica DE, Holguin F. Asthma and obesity: Mechanisms and clinical implications. Asthma Res Pract 1: 1, 2015.
 23.Balistreri CR, Caruso C, Candore G. The role of adipose tissue and adipokines in obesity‐related inflammatory diseases. Mediat Inflamm 2010: 802078, 2010.
 24.Balmain BN, Halverson QM, Tomlinson AR, Edwards T, Ganio MS, Babb TG. Obesity blunts the ventilatory response to exercise in men and women. Ann Am Thorac Soc 18: 1167‐1174, 2021.
 25.Barker DJ. The origins of the developmental origins theory. J Intern Med 261: 412‐417, 2007.
 26.Barnes PJ. Inhaled corticosteroids. Pharmaceuticals (Basel) 3: 514‐540, 2010.
 27.Barnes PJ, Adcock IM. Glucocorticoid resistance in inflammatory diseases. Lancet 373: 1905‐1917, 2009.
 28.Barros LL, Souza‐Machado A, Correa LB, Santos JS, Cruz C, Leite M, Castro L, Coelho AC, Almeida P, Cruz AA. Obesity and poor asthma control in patients with severe asthma. J Asthma 48: 171‐176, 2011.
 29.Barton JH, Ireland A, Fitzpatrick M, Kessinger C, Camp D, Weinman R, McMahon D, Leader JK, Holguin F, Wenzel SE, Morris A, Gingo MR. Adiposity influences airway wall thickness and the asthma phenotype of HIV‐associated obstructive lung disease: A cross‐sectional study. BMC Pulm Med 16: 111, 2016.
 30.Belalcazar LM, Lang W, Haffner SM, Schwenke DC, Kriska A, Balasubramanyam A, Hoogeveen RC, Pi‐Sunyer FX, Tracy RP, Ballantyne CM, Look ARG. Improving adiponectin levels in individuals with diabetes and obesity: Insights from look AHEAD. Diabetes Care 38: 1544‐1550, 2015.
 31.Bell LN, Ward JL, Degawa‐Yamauchi M, Bovenkerk JE, Jones R, Cacucci BM, Gupta CE, Sheridan C, Sheridan K, Shankar SS, Steinberg HO, March KL, Considine RV. Adipose tissue production of hepatocyte growth factor contributes to elevated serum HGF in obesity. Am J Physiol Endocrinol Metab 291: E843‐E848, 2006.
 32.Bergeron C, Tulic MK, Hamid Q. Airway remodelling in asthma: From benchside to clinical practice. Can Respir J 17: e85‐e93, 2010.
 33.Bernhard W. Lung surfactant: Function and composition in the context of development and respiratory physiology. Ann Anat 208: 146‐150, 2016.
 34.Bhammar DM, Stickford JL, Bernhardt V, Babb TG. Effect of weight loss on operational lung volumes and oxygen cost of breathing in obese women. Int J Obes 40: 998‐1004, 2016.
 35.Bhatawadekar SA, Peters U, Walsh RR, Daphtary N, MacLean ES, Mori V, Hodgdon K, Kinsey CM, Kaminsky DA, Bates JHT, Dixon AE. Central airway collapse is related to obesity independent of asthma phenotype. Respirology 26: 334‐341, 2021.
 36.Bhurosy T, Jeewon R. Overweight and obesity epidemic in developing countries: A problem with diet, physical activity, or socioeconomic status? Sci World J 2014: 964236, 2014.
 37.Blakey J, Chung LP, McDonald VM, Ruane L, Gornall J, Barton C, Bosnic‐Anticevich S, Harrington J, Hew M, Holland AE, Hopkins T, Jayaram L, Reddel H, Upham JW, Gibson PG, Bardin P. Oral corticosteroids stewardship for asthma in adults and adolescents: A position paper from the Thoracic Society of Australia and New Zealand. Respirology 26: 1112‐1130, 2021.
 38.Bodis K, Roden M. Energy metabolism of white adipose tissue and insulin resistance in humans. Eur J Clin Investig 48: e13017, 2018.
 39.Bolus WR, Kennedy AJ, Hasty AH. Obesity‐induced reduction of adipose eosinophils is reversed with low‐calorie dietary intervention. Physiol Rep 6: e13919, 2018.
 40.Boulet LP, Franssen E. Influence of obesity on response to fluticasone with or without salmeterol in moderate asthma. Respir Med 101: 2240‐2247, 2007.
 41.Boulet LP, Turcotte H, Martin J, Poirier P. Effect of bariatric surgery on airway response and lung function in obese subjects with asthma. Respir Med 106: 651‐660, 2012.
 42.Bowatte G, Bui D, Priyankara S, Lowe AJ, Perret JL, Lodge CJ, Hamilton GS, Erbas B, Thomas P, Thompson B, Schlunssen V, Martino D, Holloway JW, Svanes C, Abramson MJ, Walters EH, Dharmage SC. Parental preconception BMI trajectories from childhood to adolescence and asthma in the future offspring. J Allergy Clin Immunol S0091‐6749: 00002‐00001, 2022.
 43.Bradding P, Roberts JA, Britten KM, Montefort S, Djukanovic R, Mueller R, Heusser CH, Howarth PH, Holgate ST. Interleukin‐4, ‐5, and ‐6 and tumor necrosis factor‐alpha in normal and asthmatic airways: Evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol 10: 471‐480, 1994.
 44.Bray GA, Fruhbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet 387: 1947‐1956, 2016.
 45.Bredella MA, Gill CM, Gerweck AV, Landa MG, Kumar V, Daley SM, Torriani M, Miller KK. Ectopic and serum lipid levels are positively associated with bone marrow fat in obesity. Radiology 269: 534‐541, 2013.
 46.Brennick MJ, Pack AI, Ko K, Kim E, Pickup S, Maislin G, Schwab RJ. Altered upper airway and soft tissue structures in the New Zealand Obese mouse. Am J Respir Crit Care Med 179: 158‐169, 2009.
 47.Brown NJ, Salome CM, Berend N, Thorpe CW, King GG. Airway distensibility in adults with asthma and healthy adults, measured by forced oscillation technique. Am J Respir Crit Care Med 176: 129‐137, 2007.
 48.Bullo M, Garcia‐Lorda P, Megias I, Salas‐Salvado J. Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes Res 11: 525‐531, 2003.
 49.Calixto MC, Lintomen L, Schenka A, Saad MJ, Zanesco A, Antunes E. Obesity enhances eosinophilic inflammation in a murine model of allergic asthma. Br J Pharmacol 159: 617‐625, 2010.
 50.Campbell JE, Peckett AJ, D'Souza AM, Hawke TJ, Riddell MC. Adipogenic and lipolytic effects of chronic glucocorticoid exposure. Am J Physiol Cell Physiol 300: C198‐C209, 2011.
 51.Cannon B, Nedergaard J. Brown adipose tissue: Function and physiological significance. Physiol Rev 84: 277‐359, 2004.
 52.Cao Q, Mak KM, Ren C, Lieber CS. Leptin stimulates tissue inhibitor of metalloproteinase‐1 in human hepatic stellate cells: Respective roles of the JAK/STAT and JAK‐mediated H2O2‐dependant MAPK pathways. J Biol Chem 279: 4292‐4304, 2004.
 53.Cao W, Li M, Wu T, Feng F, Feng T, Xu Y, Sun C. alphaMSH prevents ROS‐induced apoptosis by inhibiting Foxo1/mTORC2 in mice adipose tissue. Oncotarget 8: 40872‐40884, 2017.
 54.Cardet JC, Ash S, Kusa T, Camargo CA Jr, Israel E. Insulin resistance modifies the association between obesity and current asthma in adults. Eur Respir J 48: 403‐410, 2016.
 55.Carpaij OA, Goorsenberg AWM, d'Hooghe JNS, de Bruin DM, van den Elzen RM, Nawijn MC, Annema JT, van den Berge M, Bonta PI, Burgess JK. Optical coherence tomography intensity correlates with extracellular matrix components in the airway wall. Am J Respir Crit Care Med 202: 762‐766, 2020.
 56.Carroll NG, Mutavdzic S, James AL. Distribution and degranulation of airway mast cells in normal and asthmatic subjects. Eur Respir J 19: 879‐885, 2002.
 57.Castro‐Rodriguez JA, Saglani S, Rodriguez‐Martinez CE, Oyarzun MA, Fleming L, Bush A. The relationship between inflammation and remodeling in childhood asthma: A systematic review. Pediatr Pulmonol 53: 824‐835, 2018.
 58.Cawthorn WP, Sethi JK. TNF‐alpha and adipocyte biology. FEBS Lett 582: 117‐131, 2008.
 59.Cazzola M, Rogliani P, Ora J, Calzetta L, Matera MG. Asthma and comorbidities: Recent advances. Pol Arch Intern Med 132: 16250, 2022.
 60.Chai AB, Ammit AJ, Gelissen IC. Examining the role of ABC lipid transporters in pulmonary lipid homeostasis and inflammation. Respir Res 18: 41, 2017.
 61.Chavey C, Lazennec G, Lagarrigue S, Clape C, Iankova I, Teyssier J, Annicotte JS, Schmidt J, Mataki C, Yamamoto H, Sanches R, Guma A, Stich V, Vitkova M, Jardin‐Watelet B, Renard E, Strieter R, Tuthill A, Hotamisligil GS, Vidal‐Puig A, Zorzano A, Langin D, Fajas L. CXC ligand 5 is an adipose‐tissue derived factor that links obesity to insulin resistance. Cell Metab 9: 339‐349, 2009.
 62.Chen CY, Fang QQ, Wang XF, Zhang MX, Zhao WY, Shi BH, Wu LH, Zhang LY, Tan WQ. Madelung's disease: Lipectomy or liposuction? Biomed Res Int 2018: 3975974, 2018.
 63.Chen Y, Dales R, Jiang Y. The association between obesity and asthma is stronger in nonallergic than allergic adults. Chest 130: 890‐895, 2006.
 64.Chin LY, Bosse Y, Pascoe C, Hackett TL, Seow CY, Pare PD. Mechanical properties of asthmatic airway smooth muscle. Eur Respir J 40: 45‐54, 2012.
 65.Chirinos JA, Gurubhagavatula I, Teff K, Rader DJ, Wadden TA, Townsend R, Foster GD, Maislin G, Saif H, Broderick P, Chittams J, Hanlon AL, Pack AI. CPAP, weight loss, or both for obstructive sleep apnea. N Engl J Med 370: 2265‐2275, 2014.
 66.Chylikova J, Dvorackova J, Tauber Z, Kamarad V. M1/M2 macrophage polarization in human obese adipose tissue. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 162: 79‐82, 2018.
 67.Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 46: 2347‐2355, 2005.
 68.Comberiati P, Di Cicco ME, D'Elios S, Peroni DG. How much asthma is atopic in children? Front Pediatr 5: 122, 2017.
 69.Considine RV, Nyce MR, Morales LM, Magosin SA, Sinha MK, Bauer TL, Rosato EL, Colberg J, Caro JF. Paracrine stimulation of preadipocyte‐enriched cell cultures by mature adipocytes. Am J Phys 270: E895‐E899, 1996.
 70.Contreras ZA, Chen Z, Roumeliotaki T, Annesi‐Maesano I, Baiz N, von Berg A, Bergstrom A, Crozier S, Duijts L, Ekstrom S, Eller E, Fantini MP, Kjaer HF, Forastiere F, Gerhard B, Gori D, Harskamp‐van Ginkel MW, Heinrich J, Iniguez C, Inskip H, Keil T, Kogevinas M, Lau S, Lehmann I, Maier D, van Meel ER, Mommers M, Murcia M, Porta D, Smit HA, Standl M, Stratakis N, Sunyer J, Thijs C, Torrent M, Vrijkotte TGM, Wijga AH, Berhane K, Gilliland F, Chatzi L. Does early onset asthma increase childhood obesity risk? A pooled analysis of 16 European cohorts. Eur Respir J 52: 1800504, 2018.
 71.Cristancho AG, Lazar MA. Forming functional fat: A growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol 12: 722‐734, 2011.
 72.Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360: 1509‐1517, 2009.
 73.Dagenais GR, Yi Q, Mann JF, Bosch J, Pogue J, Yusuf S. Prognostic impact of body weight and abdominal obesity in women and men with cardiovascular disease. Am Heart J 149: 54‐60, 2005.
 74.Davis KE, Neinast MD, Sun K, Skiles WM, Bills JD, Zehr JA, Zeve D, Hahner LD, Cox DW, Gent LM, Xu Y. The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis. Mol Metab 2: 227‐242, 2013.
 75.De Blasio MJ, Boije M, Kempster SL, Smith GC, Charnock‐Jones DS, Denyer A, Hughes A, Wooding FB, Blache D, Fowden AL, Forhead AJ. Leptin matures aspects of lung structure and function in the ovine fetus. Endocrinology 157: 395‐404, 2016.
 76.De Vooght V, Carlier V, Devos FC, Haenen S, Verbeken E, Nemery B, Hoet PH, Vanoirbeek JA. B‐lymphocytes as key players in chemical‐induced asthma. PLoS One 8: e83228, 2013.
 77.Deckers J, Branco Madeira F, Hammad H. Innate immune cells in asthma. Trends Immunol 34: 540‐547, 2013.
 78.Delvecchio CJ, Bilan P, Nair P, Capone JP. LXR‐induced reverse cholesterol transport in human airway smooth muscle is mediated exclusively by ABCA1. Am J Physiol Lung Cell Mol Physiol 295: L949‐L957, 2008.
 79.Desai AG, Togias A, Schechter C, Fisher B, Parow A, Skloot G. Peripheral airways dysfunction in obesity reflects increased bronchomotor tone. J Allergy Clin Immunol 135: 820‐822, 2015.
 80.d'Hooghe JNS, Goorsenberg AWM, de Bruin DM, Roelofs J, Annema JT, Bonta PI. Optical coherence tomography for identification and quantification of human airway wall layers. PLoS One 12: e0184145, 2017.
 81.Dias‐Junior SA, Reis M, de Carvalho‐Pinto RM, Stelmach R, Halpern A, Cukier A. Effects of weight loss on asthma control in obese patients with severe asthma. Eur Respir J 43: 1368‐1377, 2014.
 82.Diaz J, Farzan S. Clinical implications of the obese‐asthma phenotypes. Immunol Allergy Clin N Am 34: 739‐751, 2014.
 83.Dieudonne MN, Leneveu MC, Giudicelli Y, Pecquery R. Evidence for functional estrogen receptors alpha and beta in human adipose cells: Regional specificities and regulation by estrogens. Am J Physiol Cell Physiol 286: C655‐C661, 2004.
 84.Ding DJ, Martin JG, Macklem PT. Effects of lung volume on maximal methacholine‐induced bronchoconstriction in normal humans. J Appl Physiol (1985) 62: 1324‐1330, 1987.
 85.Dinger K, Kasper P, Hucklenbruch‐Rother E, Vohlen C, Jobst E, Janoschek R, Bae‐Gartz I, van Koningsbruggen‐Rietschel S, Plank C, Dotsch J, Alejandre Alcazar MA. Early‐onset obesity dysregulates pulmonary adipocytokine/insulin signaling and induces asthma‐like disease in mice. Sci Rep 6: 24168, 2016.
 86.Dixon AE, Pratley RE, Forgione PM, Kaminsky DA, Whittaker‐Leclair LA, Griffes LA, Garudathri J, Raymond D, Poynter ME, Bunn JY, Irvin CG. Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation. J Allergy Clin Immunol 128: 508‐515.e501‐e502, 2011.
 87.Dombret MC, Alagha K, Boulet LP, Brillet PY, Joos G, Laviolette M, Louis R, Rochat T, Soccal P, Aubier M, Chanez P. Bronchial thermoplasty: A new therapeutic option for the treatment of severe, uncontrolled asthma in adults. Eur Respir Rev 23: 510‐518, 2014.
 88.Donovan GM, Wang KCW, Shamsuddin D, Mann TS, Henry PJ, Larcombe AN, Noble PB. Pharmacological ablation of the airway smooth muscle layer‐Mathematical predictions of functional improvement in asthma. Physiol Rep 8: e14451, 2020.
 89.Dunmore SJ, Brown JE. The role of adipokines in beta‐cell failure of type 2 diabetes. J Endocrinol 216: T37‐T45, 2013.
 90.Dykstra JA, Facile T, Patrick RJ, Francis KR, Milanovich S, Weimer JM, Kota DJ. Concise review: Fat and furious: Harnessing the full potential of adipose‐derived stromal vascular fraction. Stem Cells Transl Med 6: 1096‐1108, 2017.
 91.Eising JB, Uiterwaal CS, van der Ent CK. Maternal body mass index, neonatal lung function and respiratory symptoms in childhood. Eur Respir J 46: 1342‐1349, 2015.
 92.E‐Lacerda RR, Teixeira CJ, Bordin S, Antunes E, and Anhe GF. Maternal obesity in mice exacerbates the allergic inflammatory response in the airways of male offspring. Nutrients 11: 2902, 2019.
 93.Elias I, Franckhauser S, Ferre T, Vila L, Tafuro S, Munoz S, Roca C, Ramos D, Pujol A, Riu E, Ruberte J, Bosch F. Adipose tissue overexpression of vascular endothelial growth factor protects against diet‐induced obesity and insulin resistance. Diabetes 61: 1801‐1813, 2012.
 94.Elliot JG, Donovan GM, Wang KCW, Green FHY, James AL, Noble PB. Fatty airways: Implications for obstructive disease. Eur Respir J 54: 1900857, 2019. DOI: 10.1183/13993003.00857‐2019.
 95.Elliot JG, Jones RL, Abramson MJ, Green FH, Mauad T, McKay KO, Bai TR, James AL. Distribution of airway smooth muscle remodelling in asthma: Relation to airway inflammation. Respirology 20: 66‐72, 2015.
 96.Elliot JG, Noble PB, Mauad T, Bai TR, Abramson MJ, McKay KO, Green FHY, James AL. Inflammation‐dependent and independent airway remodelling in asthma. Respirology 23: 1138‐1145, 2018.
 97.Engin A. Adipose tissue hypoxia in obesity and its impact on preadipocytes and macrophages: Hypoxia hypothesis. Adv Exp Med Biol 960: 305‐326, 2017.
 98.Evans DJ, Hoffmann RG, Kalkhoff RK, Kissebah AH. Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. J Clin Endocrinol Metab 57: 304‐310, 1983.
 99.Fahy JV. Eosinophilic and neutrophilic inflammation in asthma: Insights from clinical studies. Proc Am Thorac Soc 6: 256‐259, 2009.
 100.Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 145: 2273‐2282, 2004.
 101.Fang L, Guo F, Zhou L, Stahl R, Grams J. The cell size and distribution of adipocytes from subcutaneous and visceral fat is associated with type 2 diabetes mellitus in humans. Adipocytes 4: 273‐279, 2015.
 102.Fasshauer M, Bluher M. Adipokines in health and disease. Trends Pharmacol Sci 36: 461‐470, 2015.
 103.Fitzgerald ML, Xavier R, Haley KJ, Welti R, Goss JL, Brown CE, Zhuang DZ, Bell SA, Lu N, McKee M, Seed B, Freeman MW. ABCA3 inactivation in mice causes respiratory failure, loss of pulmonary surfactant, and depletion of lung phosphatidylglycerol. J Lipid Res 48: 621‐632, 2007.
 104.Fitzpatrick AM, Mutic AD, Mohammad AF, Stephenson ST, Grunwell JR. Obesity is associated with sustained symptomatology and unique inflammatory features in children with asthma. J Allergy Clin Immunol Pract 10: 815‐826 e812, 2022.
 105.Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 56: 1010‐1013, 2007.
 106.Franco W, Kothare A, Ronan SJ, Grekin RC, McCalmont TH. Hyperthermic injury to adipocyte cells by selective heating of subcutaneous fat with a novel radiofrequency device: Feasibility studies. Lasers Surg Med 42: 361‐370, 2010.
 107.Freitas PD, Ferreira PG, Silva AG, Stelmach R, Carvalho‐Pinto RM, Fernandes FL, Mancini MC, Sato MN, Martins MA, Carvalho CR. The role of exercise in a weight‐loss program on clinical control in obese adults with asthma. A randomized controlled trial. Am J Respir Crit Care Med 195: 32‐42, 2017.
 108.Fricker M, Gibson PG. Macrophage dysfunction in the pathogenesis and treatment of asthma. Eur Respir J 50: 1700196, 2017.
 109.Fried SK, Russell CD, Grauso NL, Brolin RE. Lipoprotein lipase regulation by insulin and glucocorticoid in subcutaneous and omental adipose tissues of obese women and men. J Clin Invest 92: 2191‐2198, 1993.
 110.Friedrich K, Sommer M, Strobel S, Thrum S, Bluher M, Wagner U, Rossol M. Perturbation of the monocyte compartment in human obesity. Front Immunol 10: 1874, 2019.
 111.Frisdal E, Le Lay S, Hooton H, Poupel L, Olivier M, Alili R, Plengpanich W, Villard EF, Gilibert S, Lhomme M, Superville A, Miftah‐Alkhair L, Chapman MJ, Dallinga‐Thie GM, Venteclef N, Poitou C, Tordjman J, Lesnik P, Kontush A, Huby T, Dugail I, Clement K, Guerin M, Le Goff W. Adipocyte ATP‐binding cassette G1 promotes triglyceride storage, fat mass growth, and human obesity. Diabetes 64: 840‐855, 2015.
 112.Frood S, Johnston LM, Matteson CL, Finegood DT. Obesity, complexity, and the role of the health system. Curr Obes Rep 2: 320‐326, 2013.
 113.Fukumura D, Incio J, Shankaraiah RC, Jain RK. Obesity and cancer: An angiogenic and inflammatory link. Microcirculation 23: 191‐206, 2016.
 114.Fullston T, Ohlsson Teague EM, Palmer NO, DeBlasio MJ, Mitchell M, Corbett M, Print CG, Owens JA, Lane M. Paternal obesity initiates metabolic disturbances in two generations of mice with incomplete penetrance to the F2 generation and alters the transcriptional profile of testis and sperm microRNA content. FASEB J 27: 4226‐4243, 2013.
 115.Fuseini H, Newcomb DC. Mechanisms driving gender differences in asthma. Curr Allergy Asthma Rep 17: 19, 2017.
 116.Garcia‐Alonso V, Titos E, Alcaraz‐Quiles J, Rius B, Lopategi A, Lopez‐Vicario C, Jakobsson PJ, Delgado S, Lozano J, Claria J. Prostaglandin E2 exerts multiple regulatory actions on human obese adipose tissue remodeling, inflammation, adaptive thermogenesis and lipolysis. PLoS One 11: e0153751, 2016.
 117.Gazzola M, Lortie K, Henry C, Mailhot‐Larouche S, Chapman DG, Couture C, Seow CY, Pare PD, King GG, Boulet LP, Bosse Y. Airway smooth muscle tone increases airway responsiveness in healthy young adults. Am J Physiol Lung Cell Mol Physiol 312: L348‐L357, 2017.
 118.Geng B, Dixon AE, Ko J, Janampally P, Haselkorn T, Holweg CTJ, Casale TB, Jarjour N. Impact of body mass index on omalizumab response in adults with moderate‐to‐severe allergic asthma. Ann Allergy Asthma Immunol 128: 553‐560, 2022.
 119.Genta PR, Schorr F, Eckert DJ, Gebrim E, Kayamori F, Moriya HT, Malhotra A, Lorenzi‐Filho G. Upper airway collapsibility is associated with obesity and hyoid position. Sleep 37: 1673‐1678, 2014.
 120.Gibeon D, Batuwita K, Osmond M, Heaney LG, Brightling CE, Niven R, Mansur A, Chaudhuri R, Bucknall CE, Rowe A, Guo Y, Bhavsar PK, Chung KF, Menzies‐Gow A. Obesity‐associated severe asthma represents a distinct clinical phenotype: Analysis of the British Thoracic Society Difficult Asthma Registry Patient cohort according to BMI. Chest 143: 406‐414, 2013.
 121.Gibson PG, Yang IA, Upham JW, Reynolds PN, Hodge S, James AL, Jenkins C, Peters MJ, Marks GB, Baraket M, Powell H, Taylor SL, Leong LEX, Rogers GB, Simpson JL. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): A randomised, double‐blind, placebo‐controlled trial. Lancet 390: 659‐668, 2017.
 122.Giesler A, Mukherjee M, Radford K, Janssen L, Nair P. Modulation of human airway smooth muscle biology by human adipocytes. Respir Res 19: 33, 2018.
 123.Gilsanz V, Hu HH, Kajimura S. Relevance of brown adipose tissue in infancy and adolescence. Pediatr Res 73: 3‐9, 2013.
 124.Girodet PO, Dournes G, Thumerel M, Begueret H, Dos Santos P, Ozier A, Dupin I, Trian T, Montaudon M, Laurent F, Marthan R, Berger P. Calcium channel blocker reduces airway remodeling in severe asthma. A proof‐of‐concept study. Am J Respir Crit Care Med 191: 876‐883, 2015.
 125.Glimcher LH, Lee AH. From sugar to fat: How the transcription factor XBP1 regulates hepatic lipogenesis. Ann N Y Acad Sci 1173 (Suppl 1): E2‐E9, 2009.
 126.Gonzales AM, Orlando RA. Role of adipocyte‐derived lipoprotein lipase in adipocyte hypertrophy. Nutr Metab (Lond) 4: 22, 2007.
 127.Grasemann H, Holguin F. Oxidative stress and obesity‐related asthma. Paediatr Respir Rev 37: 18‐21, 2021.
 128.Green FH, Williams DJ, James A, McPhee LJ, Mitchell I, Mauad T. Increased myoepithelial cells of bronchial submucosal glands in fatal asthma. Thorax 65: 32‐38, 2010.
 129.Griffiths PS, Walton C, Samsell L, Perez MK, Piedimonte G. Maternal high‐fat hypercaloric diet during pregnancy results in persistent metabolic and respiratory abnormalities in offspring. Pediatr Res 79: 278‐286, 2016.
 130.Hadda V, Khilnani GC. Lipoid pneumonia: An overview. Expert Rev Respir Med 4: 799‐807, 2010.
 131.Hammarstedt A, Gogg S, Hedjazifar S, Nerstedt A, Smith U. Impaired adipogenesis and dysfunctional adipose tissue in human hypertrophic obesity. Physiol Rev 98: 1911‐1941, 2018.
 132.Han J, Nguyen J, Kim Y, Geng B, Romanowski G, Alejandro L, Proudfoot J, Xu R, Leibel S. Effect of inhaled corticosteroid use on weight (BMI) in pediatric patients with moderate‐severe asthma. J Asthma 56: 263‐269, 2019.
 133.Harkins JM, Ahmad B. Anatomy, abdomen and pelvis, portal venous system (hepatic portal system). In: StatPearls. Treasure Island, FL: StatPearls Publishing, 2020.
 134.Harpsoe MC, Basit S, Bager P, Wohlfahrt J, Benn CS, Nohr EA, Linneberg A, Jess T. Maternal obesity, gestational weight gain, and risk of asthma and atopic disease in offspring: A study within the Danish National Birth Cohort. J Allergy Clin Immunol 131: 1033‐1040, 2013.
 135.Harskamp‐van Ginkel MW, London SJ, Magnus MC, Gademan MG, Vrijkotte TG. A study on mediation by offspring BMI in the association between maternal obesity and child respiratory outcomes in the amsterdam born and their development study cohort. PLoS One 10: e0140641, 2015.
 136.Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS. Increased adipose tissue in male and female estrogen receptor‐alpha knockout mice. Proc Natl Acad Sci U S A 97: 12729‐12734, 2000.
 137.Heldstab SA, van Schaik CP, Isler K. Getting fat or getting help? How female mammals cope with energetic constraints on reproduction. Front Zool 14: 29, 2017.
 138.Herbst KL. Subcutaneous adipose tissue diseases: Dercum disease, lipedema, familial multiple lipomatosis, and madelung disease. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Dungan K, Grossman A, Hershman JM, Kaltsas G, Koch C, Kopp P, Korbonits M, McLachlan R, Morley JE, New M, Perreault L, Purnell J, Rebar R, Singer F, Trence DL, Vinik A, Wilson DP, editors. Endotext. South Dartmouth, MA: MDText.com, Inc., 2000.
 139.Heyob KM, Mieth S, Sugar SS, Graf AE, Lallier SW, Britt RD Jr, Rogers LK. Maternal high‐fat diet alters lung development and function in the offspring. Am J Physiol Lung Cell Mol Physiol 317: L167‐L174, 2019.
 140.Hinkle SN, Rawal S, Liu D, Chen J, Tsai MY, Zhang C. Maternal adipokines longitudinally measured across pregnancy and their associations with neonatal size, length, and adiposity. Int J Obes 43: 1422‐1434, 2019.
 141.Hjellvik V, Tverdal A, Furu K. Body mass index as predictor for asthma: A cohort study of 118, 723 males and females. Eur Respir J 35: 1235‐1242, 2010.
 142.Holguin F, Bleecker ER, Busse WW, Calhoun WJ, Castro M, Erzurum SC, Fitzpatrick AM, Gaston B, Israel E, Jarjour NN, Moore WC, Peters SP, Yonas M, Teague WG, Wenzel SE. Obesity and asthma: An association modified by age of asthma onset. J Allergy Clin Immunol 127: 1486‐1493 e1482, 2011.
 143.Hong EG, Ko HJ, Cho YR, Kim HJ, Ma Z, Yu TY, Friedline RH, Kurt‐Jones E, Finberg R, Fischer MA, Granger EL, Norbury CC, Hauschka SD, Philbrick WM, Lee CG, Elias JA, Kim JK. Interleukin‐10 prevents diet‐induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes 58: 2525‐2535, 2009.
 144.Hotamisligil GS. Inflammation and metabolic disorders. Nature 444: 860‐867, 2006.
 145.Hudgins LC, Hellerstein MK, Seidman CE, Neese RA, Tremaroli JD, Hirsch J. Relationship between carbohydrate‐induced hypertriglyceridemia and fatty acid synthesis in lean and obese subjects. J Lipid Res 41: 595‐604, 2000.
 146.Ibrahim MM. Subcutaneous and visceral adipose tissue: Structural and functional differences. Obes Rev 11: 11‐18, 2010.
 147.Ignacio RM, Kim CS, Kim SK. Immunological profiling of obesity. J Lifestyle Med 4: 1‐7, 2014.
 148.Ikeda K, Maretich P, Kajimura S. The common and distinct features of brown and beige adipocytes. Trends Endocrinol Metab 29: 191‐200, 2018.
 149.Ilmarinen P, Pardo A, Tuomisto LE, Vahatalo I, Niemela O, Nieminen P, Kankaanranta H. Long‐term prognosis of new adult‐onset asthma in obese patients. Eur Respir J 57: 2001209, 2021.
 150.Ip BC, Li N, Jackson‐Browne M, Eliot M, Xu Y, Chen A, Lanphear BP, Spanier AJ, Braun JM. Does fetal leptin and adiponectin influence children's lung function and risk of wheeze? J Dev Orig Health Dis 12: 570‐577, 2021.
 151.Ishmael FT. The inflammatory response in the pathogenesis of asthma. J Am Osteopath Assoc 111: S11‐S17, 2011.
 152.James AL, Bai TR, Mauad T, Abramson MJ, Dolhnikoff M, McKay KO, Maxwell PS, Elliot JG, Green FH. Airway smooth muscle thickness in asthma is related to severity but not duration of asthma. Eur Respir J 34: 1040‐1045, 2009.
 153.James AL, Elliot JG, Jones RL, Carroll ML, Mauad T, Bai TR, Abramson MJ, McKay KO, Green FH. Airway smooth muscle hypertrophy and hyperplasia in asthma. Am J Respir Crit Care Med 185: 1058‐1064, 2012.
 154.James AL, Pare PD, Hogg JC. The mechanics of airway narrowing in asthma. Am Rev Respir Dis 139: 242‐246, 1989.
 155.Jensen ME, Gibson PG, Collins CE, Hilton JM, Wood LG. Diet‐induced weight loss in obese children with asthma: A randomized controlled trial. Clin Exp Allergy 43: 775‐784, 2013.
 156.Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE, Cushman SW, Periwal V. Hypertrophy and/or hyperplasia: Dynamics of adipose tissue growth. PLoS Comput Biol 5: e1000324, 2009.
 157.Johannessen A, Lonnebotn M, Calciano L, Benediktsdottir B, Bertelsen RJ, Braback L, Dharmage S, Franklin KA, Gislason T, Holm M, Janson C, Jarvis D, Jogi R, Kim JL, Kirkeleit J, Lodge C, Malinovschi A, Martinez‐Moratalla J, Nilsen RM, Pereira‐Vega A, Real FG, Schlunssen V, Accordini S, Svanes C. Being overweight in childhood, puberty, or early adulthood: Changing asthma risk in the next generation? J Allergy Clin Immunol 145: 791‐799 e794, 2020.
 158.John K, Marino JS, Sanchez ER, Hinds TD Jr. The glucocorticoid receptor: Cause of or cure for obesity? Am J Physiol Endocrinol Metab 310: E249‐E257, 2016.
 159.Johnson JB, Summer W, Cutler RG, Martin B, Hyun DH, Dixit VD, Pearson M, Nassar M, Telljohann R, Maudsley S, Carlson O, John S, Laub DR, Mattson MP. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med 42: 665‐674, 2007.
 160.Johnson O, Gerald LB, Harvey J, Roy G, Hazucha H, Large C, Burke A, McCormack M, Wise RA, Holbrook JT, Dixon AE. An online weight loss intervention for people with obesity and poorly controlled asthma. J Allergy Clin Immunol Pract 10: 1577‐1586e3, 2022.
 161.Jones RL, Nzekwu MM. The effects of body mass index on lung volumes. Chest 130: 827‐833, 2006.
 162.Juge‐Aubry CE, Somm E, Pernin A, Alizadeh N, Giusti V, Dayer JM, Meier CA. Adipose tissue is a regulated source of interleukin‐10. Cytokine 29: 270‐274, 2005.
 163.Jung J, Kim SH, Lee HS, Choi GS, Jung YS, Ryu DH, Park HS, Hwang GS. Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis. Clin Exp Allergy 43: 425‐433, 2013.
 164.Kaminsky DA, Chapman DG, Holbrook JT, Henderson RJ, Sugar EA, Mastronarde J, Teague WG, Busk M, Sumino K, Dixon AE, Wise RA, Irvin CG. Older age and obesity are associated with increased airway closure in response to methacholine in patients with asthma. Respirology 24: 638‐645, 2019.
 165.Kang YE, Kim JM, Joung KH, Lee JH, You BR, Choi MJ, Ryu MJ, Ko YB, Lee MA, Lee J, Ku BJ, Shong M, Lee KH, Kim HJ. The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity‐associated insulin resistance in modest obesity and early metabolic dysfunction. PLoS One 11: e0154003, 2016.
 166.Karatzi K, Moschonis G, Polychronopoulou MC, Chrousos GP, Lionis C, Manios Y, Healthy Growth Study group. Cutoff points of waist circumference and trunk and visceral fat for identifying children with elevated inflammation markers and adipokines: The Healthy Growth Study. Nutrition 32: 1063‐1067, 2016.
 167.Kay AB. The role of T lymphocytes in asthma. Chem Immunol Allergy 91: 59‐75, 2006.
 168.Kennedy MA, Barrera GC, Nakamura K, Baldan A, Tarr P, Fishbein MC, Frank J, Francone OL, Edwards PA. ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab 1: 121‐131, 2005.
 169.Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89: 2548‐2556, 2004.
 170.Khan M, Joseph F. Adipose tissue and adipokines: The association with and application of adipokines in obesity. Scientifica (Cairo) 2014: 328592, 2014.
 171.Khaodhiar L, McCowen KC, Blackburn GL. Obesity and its comorbid conditions. Clin Cornerstone 2: 17‐31, 1999.
 172.Khurana S, Paggiaro P, Buhl R, Bernstein JA, Haddon J, Unseld A, Engel M, Casale TB, Dixon AE. Tiotropium reduces airflow obstruction in asthma patients, independent of body mass index. J Allergy Clin Immunol Pract 7: 2425‐2428 e2427, 2019.
 173.Kielar D, Dietmaier W, Langmann T, Aslanidis C, Probst M, Naruszewicz M, Schmitz G. Rapid quantification of human ABCA1 mRNA in various cell types and tissues by real‐time reverse transcription‐PCR. Clin Chem 47: 2089‐2097, 2001.
 174.Kim D, Kim WR. Nonobese fatty liver disease. Clin Gastroenterol Hepatol 15: 474‐485, 2017.
 175.Kim JH, Jang YJ. Role of natural killer cells in airway inflammation. Allergy, Asthma Immunol Res 10: 448‐456, 2018.
 176.Kloting N, Fasshauer M, Dietrich A, Kovacs P, Schon MR, Kern M, Stumvoll M, Bluher M. Insulin‐sensitive obesity. Am J Physiol Endocrinol Metab 299: E506‐E515, 2010.
 177.Knobloch J, Yanik SD, Korber S, Stoelben E, Jungck D, Koch A. TNFalpha‐induced airway smooth muscle cell proliferation depends on endothelin receptor signaling, GM‐CSF and IL‐6. Biochem Pharmacol 116: 188‐199, 2016.
 178.Koster A, Murphy RA, Eiriksdottir G, Aspelund T, Sigurdsson S, Lang TF, Gudnason V, Launer LJ, Harris TB. Fat distribution and mortality: The AGES‐Reykjavik Study. Obesity (Silver Spring) 23: 893‐897, 2015.
 179.Kudo M, Ishigatsubo Y, Aoki I. Pathology of asthma. Front Microbiol 4: 263, 2013.
 180.Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat is an independent predictor of all‐cause mortality in men. Obesity (Silver Spring) 14: 336‐341, 2006.
 181.Kuwano K, Bosken CH, Pare PD, Bai TR, Wiggs BR, Hogg JC. Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 148: 1220‐1225, 1993.
 182.Kwon H, Kim D, Kim JS. Body fat distribution and the risk of incident metabolic syndrome: A longitudinal cohort study. Sci Rep 7: 10955, 2017.
 183.LaCoursiere DY, Bloebaum L, Duncan JD, Varner MW. Population‐based trends and correlates of maternal overweight and obesity, Utah 1991‐2001. Am J Obstet Gynecol 192: 832‐839, 2005.
 184.Landecho MF, Tuero C, Valenti V, Bilbao I, de la Higuera M, Fruhbeck G. Relevance of leptin and other adipokines in obesity‐associated cardiovascular risk. Nutrients 11: 2664, 2019.
 185.Langton D, Bennetts K, Noble P, Plummer V, Thien F. Bronchial thermoplasty reduces airway resistance. Respir Res 21: 76, 2020.
 186.Larsen TM, Toubro S, van Baak MA, Gottesdiener KM, Larson P, Saris WH, Astrup A. Effect of a 28‐d treatment with L‐796568, a novel beta(3)‐adrenergic receptor agonist, on energy expenditure and body composition in obese men. Am J Clin Nutr 76: 780‐788, 2002.
 187.Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: A global perspective. Semin Liver Dis 28: 339‐350, 2008.
 188.de Oliveira Leal V, Mafra D. Adipokines in obesity. Clin Chim Acta 419: 87‐94, 2013.
 189.Lecomte V, Maloney CA, Wang KW, Morris MJ. Effects of paternal obesity on growth and adiposity of male rat offspring. Am J Physiol Endocrinol Metab 312: E117‐E125, 2017.
 190.Leddy MA, Power ML, Schulkin J. The impact of maternal obesity on maternal and fetal health. Rev Obstet Gynecol 1: 170‐178, 2008.
 191.Lee BC, Kim MS, Pae M, Yamamoto Y, Eberle D, Shimada T, Kamei N, Park HS, Sasorith S, Woo JR, You J, Mosher W, Brady HJ, Shoelson SE, Lee J. Adipose natural killer cells regulate adipose tissue macrophages to promote insulin resistance in obesity. Cell Metab 23: 685‐698, 2016.
 192.Leitner BP, Huang S, Brychta RJ, Duckworth CJ, Baskin AS, McGehee S, Tal I, Dieckmann W, Gupta G, Kolodny GM, Pacak K, Herscovitch P, Cypess AM, Chen KY. Mapping of human brown adipose tissue in lean and obese young men. Proc Natl Acad Sci U S A 114: 8649‐8654, 2017.
 193.Li HX, Zhang F, Zhao D, Xin Z, Guo SQ, Wang SM, Zhang JJ, Wang J, Li Y, Yang GR, Yang JK. Neck circumference as a measure of neck fat and abdominal visceral fat in Chinese adults. BMC Public Health 14: 311, 2014.
 194.Li J, Quirk BC, Noble PB, Kirk RW, Sampson DD, McLaughlin RA. Flexible needle with integrated optical coherence tomography probe for imaging during transbronchial tissue aspiration. J Biomed Opt 22: 1‐5, 2017.
 195.Li Q, Karnowski K, Noble PB, Cairncross A, James A, Villiger M, Sampson DD. Robust reconstruction of local optic axis orientation with fiber‐based polarization‐sensitive optical coherence tomography. Biomed Opt Express 9: 5437‐5455, 2018.
 196.Lichtenauer M, Franz M, Fritzenwanger M, Figulla HR, Gerdes N, Jung C. Elevated plasma levels of interleukin‐12p40 and interleukin‐16 in overweight adolescents. Biomed Res Int 2015: 940910, 2015.
 197.Lin CK, Lin YH, Huang TC, Shi CS, Yang CT, Yang YL. VEGF mediates fat embolism‐induced acute lung injury via VEGF receptor 2 and the MAPK cascade. Sci Rep 9: 11713, 2019.
 198.Lin G, Wang G, Banie L, Ning H, Shindel AW, Fandel TM, Lue TF, Lin CS. Treatment of stress urinary incontinence with adipose tissue‐derived stem cells. Cytotherapy 12: 88‐95, 2010.
 199.Liu W, Zhou H, Zhang Q, Zhang R, Willard B, Liu CL, Kang Z. IL‐1R‐IRAKM‐Slc25a1 signaling axis reprograms lipogenesis in adipocytes to promote diet‐induced obesity in mice. Nat Commun 13: 2748, 2022.
 200.Longo M, Zatterale F, Naderi J, Parrillo L, Formisano P, Raciti GA, Beguinot F, Miele C. Adipose tissue dysfunction as determinant of obesity‐associated metabolic complications. Int J Mol Sci 20: 2358, 2019.
 201.Lonn M, Mehlig K, Bengtsson C, Lissner L. Adipocyte size predicts incidence of type 2 diabetes in women. FASEB J 24: 326‐331, 2010.
 202.Lovejoy JC, Champagne CM, de Jonge L, Xie H, Smith SR. Increased visceral fat and decreased energy expenditure during the menopausal transition. Int J Obes 32: 949‐958, 2008.
 203.Luce JM, Culver BH. Respiratory muscle function in health and disease. Chest 81: 82‐90, 1982.
 204.Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117: 175‐184, 2007.
 205.Luna‐Pech JA, Torres‐Mendoza BM, Luna‐Pech JA, Garcia‐Cobas CY, Navarrete‐Navarro S, Elizalde‐Lozano AM. Normocaloric diet improves asthma‐related quality of life in obese pubertal adolescents. Int Arch Allergy Immunol 163: 252‐258, 2014.
 206.Luzak A, Karrasch S, Thorand B, Nowak D, Holle R, Peters A, Schulz H. Association of physical activity with lung function in lung‐healthy German adults: Results from the KORA FF4 study. BMC Pulm Med 17: 215, 2017.
 207.Macklem PT. Factors determining bronchial smooth muscle shortening. Am Rev Respir Dis 143: S47‐S48, 1991.
 208.Madani R, Karastergiou K, Ogston NC, Miheisi N, Bhome R, Haloob N, Tan GD, Karpe F, Malone‐Lee J, Hashemi M, Jahangiri M, Mohamed‐Ali V. RANTES release by human adipose tissue in vivo and evidence for depot‐specific differences. Am J Physiol Endocrinol Metab 296: E1262‐E1268, 2009.
 209.Mai XM, Becker AB, Sellers EA, Liem JJ, Kozyrskyj AL. The relationship of breast‐feeding, overweight, and asthma in preadolescents. J Allergy Clin Immunol 120: 551‐556, 2007.
 210.Malli F, Papaioannou AI, Gourgoulianis KI, Daniil Z. The role of leptin in the respiratory system: An overview. Respir Res 11: 152, 2010.
 211.Maniscalco M, Zamparelli AS, Vitale DF, Faraone S, Molino A, Zedda A, Motta A. Long‐term effect of weight loss induced by bariatric surgery on asthma control and health related quality of life in asthmatic patients with severe obesity: A pilot study. Respir Med 130: 69‐74, 2017.
 212.Marijsse GS, Seys SF, Schelpe AS, Dilissen E, Goeminne P, Dupont LJ, Ceuppens JL, Bullens DM. Obese individuals with asthma preferentially have a high IL‐5/IL‐17A/IL‐25 sputum inflammatory pattern. Am J Respir Crit Care Med 189: 1284‐1285, 2014.
 213.Marko M, Pawliczak R. Obesity and asthma: Risk, control and treatment. Postepy Dermatol Alergol 35: 563‐571, 2018.
 214.Matoba A, Matsuyama N, Shibata S, Masaki E, Emala CW Sr, Mizuta K. The free fatty acid receptor 1 promotes airway smooth muscle cell proliferation through MEK/ERK and PI3K/Akt signaling pathways. Am J Physiol Lung Cell Mol Physiol 314: L333‐L348, 2018.
 215.Mazini L, Rochette L, Amine M, Malka G. Regenerative capacity of adipose derived stem cells (ADSCs), comparison with mesenchymal stem cells (MSCs). Int J Mol Sci 20: 2523, 2019.
 216.McCulloch LJ, Rawling TJ, Sjoholm K, Franck N, Dankel SN, Price EJ, Knight B, Liversedge NH, Mellgren G, Nystrom F, Carlsson LM, Kos K. COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity. Endocrinology 156: 134‐146, 2015.
 217.McDevitt RM, Bott SJ, Harding M, Coward WA, Bluck LJ, Prentice AM. De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women. Am J Clin Nutr 74: 737‐746, 2001.
 218.McGillick EV, Lock MC, Orgeig S, Morrison JL. Maternal obesity mediated predisposition to respiratory complications at birth and in later life: Understanding the implications of the obesogenic intrauterine environment. Paediatr Respir Rev 21: 11‐18, 2017.
 219.Menezes S, Melandri D, Anselmi G, Perchet T, Loschko J, Dubrot J, Patel R, Gautier EL, Hugues S, Longhi MP, Henry JY, Quezada SA, Lauvau G, Lennon‐Dumenil AM, Gutierrez‐Martinez E, Bessis A, Gomez‐Perdiguero E, Jacome‐Galarza CE, Garner H, Geissmann F, Golub R, Nussenzweig MC, Guermonprez P. The heterogeneity of ly6C(hi) monocytes controls their differentiation into iNOS(+) macrophages or monocyte‐derived dendritic cells. Immunity 45: 1205‐1218, 2016.
 220.Mensink‐Bout SM, Santos S, van Meel ER, Oei EHG, de Jongste JC, Jaddoe VWV, Duijts L. General and organ fat assessed by magnetic resonance imaging and respiratory outcomes in childhood. Am J Respir Crit Care Med 201: 348‐355, 2020.
 221.Milde R, Ritter J, Tennent GA, Loesch A, Martinez FO, Gordon S, Pepys MB, Verschoor A, Helming L. Multinucleated giant cells are specialized for complement‐mediated phagocytosis and large target destruction. Cell Rep 13: 1937‐1948, 2015.
 222.Miller AM, Asquith DL, Hueber AJ, Anderson LA, Holmes WM, McKenzie AN, Xu D, Sattar N, McInnes IB, Liew FY. Interleukin‐33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res 107: 650‐658, 2010.
 223.Miranda C, Busacker A, Balzar S, Trudeau J, Wenzel SE. Distinguishing severe asthma phenotypes: Role of age at onset and eosinophilic inflammation. J Allergy Clin Immunol 113: 101‐108, 2004.
 224.Mizuta K, Zhang Y, Mizuta F, Hoshijima H, Shiga T, Masaki E, Emala CW Sr. Novel identification of the free fatty acid receptor FFAR1 that promotes contraction in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 309: L970‐L982, 2015.
 225.Moitra S, Carsin AE, Abramson MJ, Accordini S, Amaral AFS, Anto J, Bono R, Casas Ruiz L, Cerveri I, Chatzi L, Demoly P, Dorado‐Arenas S, Forsberg B, Gilliland F, Gislason T, Gullon JA, Heinrich J, Holm M, Janson C, Jogi R, Gomez Real F, Jarvis D, Leynaert B, Nowak D, Probst‐Hensch N, Sanchez‐Ramos JL, Raherison‐Semjen C, Siroux V, Guerra S, Kogevinas M, Garcia‐Aymerich J. Long‐term effect of asthma on the development of obesity among adults: An international cohort study, ECRHS. Thorax, 2022. DOI: 10.1136/thoraxjnl-2021-217867
 226.Montani JP, Carroll JF, Dwyer TM, Antic V, Yang Z, Dulloo AG. Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases. Int J Obes Relat Metab Disord 28 (Suppl 4): S58‐S65, 2004.
 227.Moore PE, Church TL, Chism DD, Panettieri RA Jr, Shore SA. IL‐13 and IL‐4 cause eotaxin release in human airway smooth muscle cells: A role for ERK. Am J Physiol Lung Cell Mol Physiol 282: L847‐L853, 2002.
 228.Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D'Agostino R Jr, Castro M, Curran‐Everett D, Fitzpatrick AM, Gaston B, Jarjour NN, Sorkness R, Calhoun WJ, Chung KF, Comhair SA, Dweik RA, Israel E, Peters SP, Busse WW, Erzurum SC, Bleecker ER, National Heart L, Blood Institute's Severe Asthma Research P. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 181: 315‐323, 2010.
 229.Mortimore IL, Marshall I, Wraith PK, Sellar RJ, Douglas NJ. Neck and total body fat deposition in nonobese and obese patients with sleep apnea compared with that in control subjects. Am J Respir Crit Care Med 157: 280‐283, 1998.
 230.Mosen DM, Schatz M, Magid DJ, Camargo CA Jr. The relationship between obesity and asthma severity and control in adults. J Allergy Clin Immunol 122: 507‐511 e506, 2008.
 231.Moynihan BJ, Tolloczko B, El Bassam S, Ferraro P, Michoud MC, Martin JG, Laberge S. IFN‐gamma, IL‐4 and IL‐13 modulate responsiveness of human airway smooth muscle cells to IL‐13. Respir Res 9: 84, 2008.
 232.Murdoch JR, Lloyd CM. Chronic inflammation and asthma. Mutat Res 690: 24‐39, 2010.
 233.Nagayama M, Uchida T, Gohara K. Temporal and spatial variations of lipid droplets during adipocyte division and differentiation. J Lipid Res 48: 9‐18, 2007.
 234.Naghshin J, Wang L, Pare PD, Seow CY. Adaptation to chronic length change in explanted airway smooth muscle. J Appl Physiol (1985) 95: 448‐453; discussion 435, 2003.
 235.Nair P, Radford K, Fanat A, Janssen LJ, Peters‐Golden M, Cox PG. The effects of leptin on airway smooth muscle responses. Am J Respir Cell Mol Biol 39: 475‐481, 2008.
 236.Nasiri Kalmarzi R, Ataee P, Mansori M, Moradi G, Ahmadi S, Kaviani Z, Khalafi B, Kooti W. Serum levels of adiponectin and leptin in asthmatic patients and its relation with asthma severity, lung function and BMI. Allergol Immunopathol (Madr) 45: 258‐264, 2017.
 237.Nishi H, Higashihara T, Inagi R. Lipotoxicity in kidney, heart, and skeletal muscle dysfunction. Nutrients 11: 1664, 2019.
 238.Noble PB, Jones RL, Cairncross A, Elliot JG, Mitchell HW, James AL, McFawn PK. Airway narrowing and bronchodilation to deep inspiration in bronchial segments from subjects with and without reported asthma. J Appl Physiol (1985) 114: 1460‐1471, 2013.
 239.Noble PB, Sharma A, McFawn PK, Mitchell HW. Airway narrowing in porcine bronchi with and without lung parenchyma. Eur Respir J 26: 804‐811, 2005.
 240.Noble PB, West AR, McLaughlin RA, Armstrong JJ, Becker S, McFawn PK, Williamson JP, Eastwood PR, Hillman DR, Sampson DD, Mitchell HW. Airway narrowing assessed by anatomical optical coherence tomography in vitro: Dynamic airway wall morphology and function. J Appl Physiol (1985) 108: 401‐411, 2010.
 241.Norel X, Walch L, Labat C, Gascard JP, Dulmet E, Brink C. Prostanoid receptors involved in the relaxation of human bronchial preparations. Br J Pharmacol 126: 867‐872, 1999.
 242.Okamoto Y, Folco EJ, Minami M, Wara AK, Feinberg MW, Sukhova GK, Colvin RA, Kihara S, Funahashi T, Luster AD, Libby P. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T‐lymphocyte recruitment in atherogenesis. Circ Res 102: 218‐225, 2008.
 243.Okuno Y, Fukuhara A, Hashimoto E, Kobayashi H, Kobayashi S, Otsuki M, Shimomura I. Oxidative stress inhibits healthy adipose expansion through suppression of SREBF1‐mediated lipogenic pathway. Diabetes 67: 1113‐1127, 2018.
 244.Orfanos S, Jude J, Deeney BT, Cao G, Rastogi D, van Zee M, Pushkarsky I, Munoz HE, Damoiseaux R, Di Carlo D, Panettieri RA Jr. Obesity increases airway smooth muscle responses to contractile agonists. Am J Physiol Lung Cell Mol Physiol 315: L673‐L681, 2018.
 245.Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11: 85‐97, 2011.
 246.Ouldamer L, Jourdan M, Pinault M, Arbion F, Goupille C. Accumulation of arachidonic acid, precursor of pro‐inflammatory eicosanoids, in adipose tissue of obese women: Association with breast cancer aggressiveness indicators. Biomedicine 10: 995, 2022.
 247.Palmer BF, Clegg DJ. The sexual dimorphism of obesity. Mol Cell Endocrinol 402: 113‐119, 2015.
 248.Patel SP, Rodriguez A, Little MP, Elliott P, Pekkanen J, Hartikainen AL, Pouta A, Laitinen J, Harju T, Canoy D, Jarvelin MR. Associations between pre‐pregnancy obesity and asthma symptoms in adolescents. J Epidemiol Community Health 66: 809‐814, 2012.
 249.Pelosi P, Croci M, Ravagnan I, Tredici S, Pedoto A, Lissoni A, Gattinoni L. The effects of body mass on lung volumes, respiratory mechanics, and gas exchange during general anesthesia. Anesth Analg 87: 654‐660, 1998.
 250.Perez MK, Piedimonte G. Metabolic asthma: Is there a link between obesity, diabetes, and asthma? Immunol Allergy Clin N Am 34: 777‐784, 2014.
 251.Perkins C, Yanase N, Smulian G, Gildea L, Orekov T, Potter C, Brombacher F, Aronow B, Wills‐Karp M, Finkelman FD. Selective stimulation of IL‐4 receptor on smooth muscle induces airway hyperresponsiveness in mice. J Exp Med 208: 853‐867, 2011.
 252.Peters U, Dixon AE, Forno E. Obesity and asthma. J Allergy Clin Immunol 141: 1169‐1179, 2018.
 253.Peters U, Hernandez P, Dechman G, Ellsmere J, Maksym G. Early detection of changes in lung mechanics with oscillometry following bariatric surgery in severe obesity. Appl Physiol Nutr Metab 41: 538‐547, 2016.
 254.Peters U, Subramanian M, Chapman DG, Kaminsky DA, Irvin CG, Wise RA, Skloot GS, Bates JHT, Dixon AE. BMI but not central obesity predisposes to airway closure during bronchoconstriction. Respirology 24: 543‐550, 2019.
 255.Peters‐Golden M, Swern A, Bird SS, Hustad CM, Grant E, Edelman JM. Influence of body mass index on the response to asthma controller agents. Eur Respir J 27: 495‐503, 2006.
 256.Petruzzelli M, Schweiger M, Schreiber R, Campos‐Olivas R, Tsoli M, Allen J, Swarbrick M, Rose‐John S, Rincon M, Robertson G, Zechner R, Wagner EF. A switch from white to brown fat increases energy expenditure in cancer‐associated cachexia. Cell Metab 20: 433‐447, 2014.
 257.Pike KC, Inskip HM, Robinson SM, Cooper C, Godfrey KM, Roberts G, Lucas JS, Southampton Women's Survey Study G. The relationship between maternal adiposity and infant weight gain, and childhood wheeze and atopy. Thorax 68: 372‐379, 2013.
 258.Pinkerton JW, Kim RY, Brown AC, Rae BE, Donovan C, Mayall JR, Carroll OR, Ali MK, Scott HA, Berthon BS, Baines KJ, Starkey MR, Kermani NZ, Guo YK, Robertson AAB, O'Neill LAJ, Adcock IM, Cooper MA, Gibson PG, Wood LG, Hansbro PM, Horvat JC. Relationship between type 2 cytokine and inflammasome responses in obesity‐associated asthma. J Allergy Clin Immunol S0091‐6749: 01525‐01526, 2021.
 259.Polinski KJ, Liu J, Boghossian NS, McLain AC. Maternal obesity, gestational weight gain, and asthma in offspring. Prev Chronic Dis 14: E109, 2017.
 260.Polyzos SA, Kountouras J, Anastasilakis AD, Geladari EV, Mantzoros CS. Irisin in patients with nonalcoholic fatty liver disease. Metabolism 63: 207‐217, 2014.
 261.Possa SS, Leick EA, Prado CM, Martins MA, Tiberio IF. Eosinophilic inflammation in allergic asthma. Front Pharmacol 4: 46, 2013.
 262.Pradeepan S, Garrison G, Dixon AE. Obesity in asthma: Approaches to treatment. Curr Allergy Asthma Rep 13: 434‐442, 2013.
 263.Qiao L, Zou C, van der Westhuyzen DR, Shao J. Adiponectin reduces plasma triglyceride by increasing VLDL triglyceride catabolism. Diabetes 57: 1824‐1833, 2008.
 264.Quintar A, McArdle S, Wolf D, Marki A, Ehinger E, Vassallo M, Miller J, Mikulski Z, Ley K, Buscher K. Endothelial protective monocyte patrolling in large arteries intensified by western diet and atherosclerosis. Circ Res 120: 1789‐1799, 2017.
 265.Rastogi D, Fraser S, Oh J, Huber AM, Schulman Y, Bhagtani RH, Khan ZS, Tesfa L, Hall CB, Macian F. Inflammation, metabolic dysregulation, and pulmonary function among obese urban adolescents with asthma. Am J Respir Crit Care Med 191: 149‐160, 2015.
 266.Reichman NE, Nepomnyaschy L. Maternal pre‐pregnancy obesity and diagnosis of asthma in offspring at age 3 years. Matern Child Health J 12: 725‐733, 2008.
 267.Riis‐Vestergaard MJ, Richelsen B, Bruun JM, Li W, Hansen JB, Pedersen SB. Beta‐1 and not beta‐3 adrenergic receptors may be the primary regulator of human brown adipocyte metabolism. J Clin Endocrinol Metab 105: e994‐e1005, 2020.
 268.Robinson MB, Deshpande DA, Chou J, Cui W, Smith S, Langefeld C, Hastie AT, Bleecker ER, Hawkins GA. IL‐6 trans‐signaling increases expression of airways disease genes in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 309: L129‐L138, 2015.
 269.Rodriguez‐Hernandez H, Simental‐Mendia LE, Rodriguez‐Ramirez G, Reyes‐Romero MA. Obesity and inflammation: Epidemiology, risk factors, and markers of inflammation. Int J Endocrinol 2013: 678159, 2013.
 270.Rogliani P, Sforza M, Calzetta L. The impact of comorbidities on severe asthma. Curr Opin Pulm Med 26: 47‐55, 2020.
 271.Romero F, Shah D, Duong M, Penn RB, Fessler MB, Madenspacher J, Stafstrom W, Kavuru M, Lu B, Kallen CB, Walsh K, Summer R. A pneumocyte‐macrophage paracrine lipid axis drives the lung toward fibrosis. Am J Respir Cell Mol Biol 53: 74‐86, 2015.
 272.Romero‐Corral A, Caples SM, Lopez‐Jimenez F, Somers VK. Interactions between obesity and obstructive sleep apnea: Implications for treatment. Chest 137: 711‐719, 2010.
 273.Rosen ED, MacDougald OA. Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7: 885‐896, 2006.
 274.Rotundo L, Persaud A, Feurdean M, Ahlawat S, Kim HS. The association of leptin with severity of non‐alcoholic fatty liver disease: A population‐based study. Clin Mol Hepatol 24: 392‐401, 2018.
 275.Ruban A, Stoenchev K, Ashrafian H, Teare J. Current treatments for obesity. Clin Med (Lond) 19: 205‐212, 2019.
 276.Russo L, Lumeng CN. Properties and functions of adipose tissue macrophages in obesity. Immunology 155: 407‐417, 2018.
 277.Rytka JM, Wueest S, Schoenle EJ, Konrad D. The portal theory supported by venous drainage‐selective fat transplantation. Diabetes 60: 56‐63, 2011.
 278.Said MA, Eppinga RN, Lipsic E, Verweij N, van der Harst P. Relationship of arterial stiffness index and pulse pressure with cardiovascular disease and mortality. J Am Heart Assoc 7: e007621, 2018.
 279.Saito M, Okamatsu‐Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio‐Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M. High incidence of metabolically active brown adipose tissue in healthy adult humans: Effects of cold exposure and adiposity. Diabetes 58: 1526‐1531, 2009.
 280.Salem SA, Hwie AN, Saim A, Chee Kong CH, Sagap I, Singh R, Yusof MR, Md Zainuddin Z, Hj IR. Human adipose tissue derived stem cells as a source of smooth muscle cells in the regeneration of muscular layer of urinary bladder wall. Malays J Med Sci 20: 80‐87, 2013.
 281.Salvator H, Grassin‐Delyle S, Brollo M, Couderc LJ, Abrial C, Victoni T, Naline E, Devillier P. Adiponectin inhibits the production of TNF‐alpha, IL‐6 and chemokines by human lung macrophages. Front Pharmacol 12: 718929, 2021.
 282.Santosa S, Bush NC, Jensen MD. Acute testosterone deficiency alters adipose tissue fatty acid storage. J Clin Endocrinol Metab 102: 3056‐3064, 2017.
 283.Saunders R, Kaul H, Berair R, Gonem S, Singapuri A, Sutcliffe AJ, Chachi L, Biddle MS, Kaur D, Bourne M, Pavord ID, Wardlaw AJ, Siddiqui SH, Kay RA, Brook BS, Smallwood RH, Brightling CE. DP2 antagonism reduces airway smooth muscle mass in asthma by decreasing eosinophilia and myofibroblast recruitment. Sci Transl Med 11: eaao6451, 2019.
 284.Saxena NK, Titus MA, Ding X, Floyd J, Srinivasan S, Sitaraman SV, Anania FA. Leptin as a novel profibrogenic cytokine in hepatic stellate cells: Mitogenesis and inhibition of apoptosis mediated by extracellular regulated kinase (Erk) and Akt phosphorylation. FASEB J 18: 1612‐1614, 2004.
 285.Schittny JC. Development of the lung. Cell Tissue Res 367: 427‐444, 2017.
 286.Schmidt FM, Weschenfelder J, Sander C, Minkwitz J, Thormann J, Chittka T, Mergl R, Kirkby KC, Fasshauer M, Stumvoll M, Holdt LM, Teupser D, Hegerl U, Himmerich H. Inflammatory cytokines in general and central obesity and modulating effects of physical activity. PLoS One 10: e0121971, 2015.
 287.Schorr M, Dichtel LE, Gerweck AV, Valera RD, Torriani M, Miller KK, Bredella MA. Sex differences in body composition and association with cardiometabolic risk. Biol Sex Differ 9: 28, 2018.
 288.Schwab RJ, Pasirstein M, Pierson R, Mackley A, Hachadoorian R, Arens R, Maislin G, Pack AI. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric magnetic resonance imaging. Am J Respir Crit Care Med 168: 522‐530, 2003.
 289.Scott HA, Gibson PG, Garg ML, Pretto JJ, Morgan PJ, Callister R, Wood LG. Dietary restriction and exercise improve airway inflammation and clinical outcomes in overweight and obese asthma: A randomized trial. Clin Exp Allergy 43: 36‐49, 2013.
 290.Scott HA, Gibson PG, Garg ML, Wood LG. Airway inflammation is augmented by obesity and fatty acids in asthma. Eur Respir J 38: 594‐602, 2011.
 291.Shen W, Punyanitya M, Silva AM, Chen J, Gallagher D, Sardinha LB, Allison DB, Heymsfield SB. Sexual dimorphism of adipose tissue distribution across the lifespan: A cross‐sectional whole‐body magnetic resonance imaging study. Nutr Metab (Lond) 6: 17, 2009.
 292.Shin JH, Kim JH, Lee WY, Shim JY. The expression of adiponectin receptors and the effects of adiponectin and leptin on airway smooth muscle cells. Yonsei Med J 49: 804‐810, 2008.
 293.Shin SK, Cho HW, Song SE, Im SS, Bae JH, Song DK. Oxidative stress resulting from the removal of endogenous catalase induces obesity by promoting hyperplasia and hypertrophy of white adipocytes. Redox Biol 37: 101749, 2020.
 294.Shore SA, Schwartzman IN, Mellema MS, Flynt L, Imrich A, Johnston RA. Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol 115: 103‐109, 2005.
 295.Shore SA, Terry RD, Flynt L, Xu A, Hug C. Adiponectin attenuates allergen‐induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol 118: 389‐395, 2006.
 296.Sideleva O, Dixon AE. The many faces of asthma in obesity. J Cell Biochem 115: 421‐426, 2014.
 297.Sideleva O, Suratt BT, Black KE, Tharp WG, Pratley RE, Forgione P, Dienz O, Irvin CG, Dixon AE. Obesity and asthma: An inflammatory disease of adipose tissue not the airway. Am J Respir Crit Care Med 186: 598‐605, 2012.
 298.Sidossis LS, Porter C, Saraf MK, Borsheim E, Radhakrishnan RS, Chao T, Ali A, Chondronikola M, Mlcak R, Finnerty CC, Hawkins HK, Toliver‐Kinsky T, Herndon DN. Browning of subcutaneous white adipose tissue in humans after severe adrenergic stress. Cell Metab 22: 219‐227, 2015.
 299.Silha JV, Krsek M, Sucharda P, Murphy LJ. Angiogenic factors are elevated in overweight and obese individuals. Int J Obes 29: 1308‐1314, 2005.
 300.Silveira LS, Monteiro PA, Antunes Bde M, Seraphim PM, Fernandes RA, Christofaro DG, Freitas Junior IF. Intra‐abdominal fat is related to metabolic syndrome and non‐alcoholic fat liver disease in obese youth. BMC Pediatr 13: 115, 2013.
 301.Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: Assessment and identification using induced sputum. Respirology 11: 54‐61, 2006.
 302.Simpson L, Mukherjee S, Cooper MN, Ward KL, Lee JD, Fedson AC, Potter J, Hillman DR, Eastwood P, Palmer LJ, Kirkness J. Sex differences in the association of regional fat distribution with the severity of obstructive sleep apnea. Sleep 33: 467‐474, 2010.
 303.Singh P, Zhang Y, Sharma P, Covassin N, Soucek F, Friedman PA, Somers VK. Statins decrease leptin expression in human white adipocytes. Physiol Rep 6: e13566, 2018.
 304.Skurk T, Alberti‐Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 92: 1023‐1033, 2007.
 305.Smoothy J, Larcombe AN, Chivers EK, Matthews VB, Gorman S. Maternal high fat diet compromises survival and modulates lung development of offspring, and impairs lung function of dams (female mice). Respir Res 20: 21, 2019.
 306.Song Y, Yu Y, Wang D, Chai S, Liu D, Xiao X, Huang Y. Maternal high‐fat diet feeding during pregnancy and lactation augments lung inflammation and remodeling in the offspring. Respir Physiol Neurobiol 207: 1‐6, 2015.
 307.Sood A, Cui X, Qualls C, Beckett WS, Gross MD, Steffes MW, Smith LJ, Jacobs DR Jr. Association between asthma and serum adiponectin concentration in women. Thorax 63: 877‐882, 2008.
 308.Souza de Almeida AH, Rodrigues Filho EA, Lubambo Costa E, de Albuquerque CG, Sarinho ESC, Medeiros Peixoto D, Dela Bianca ACC, Correia Junior MAV, Rizzo JA. Obesity is a risk factor for exercise‐induced bronchospasm in asthmatic adolescents. Pediatr Pulmonol 55: 1916‐1923, 2020.
 309.Spalding KL, Bernard S, Naslund E, Salehpour M, Possnert G, Appelsved L, Fu KY, Alkass K, Druid H, Thorell A, Ryden M, Arner P. Impact of fat mass and distribution on lipid turnover in human adipose tissue. Nat Commun 8: 15253, 2017.
 310.Sparrenberger K, Sbaraini M, Cureau FV, Telo GH, Bahia L, Schaan BD. Higher adiponectin concentrations are associated with reduced metabolic syndrome risk independently of weight status in Brazilian adolescents. Diabetol Metab Syndr 11: 40, 2019.
 311.Spencer M, Unal R, Zhu B, Rasouli N, McGehee RE Jr, Peterson CA, Kern PA. Adipose tissue extracellular matrix and vascular abnormalities in obesity and insulin resistance. J Clin Endocrinol Metab 96: E1990‐E1998, 2011.
 312.Srivastava S, Veech RL. Brown and brite: The fat soldiers in the anti‐obesity fight. Front Physiol 10: 38, 2019.
 313.Stamatiou R, Paraskeva E, Gourgoulianis K, Molyvdas PA, Hatziefthimiou A. Cytokines and growth factors promote airway smooth muscle cell proliferation. ISRN Inflamm 2012: 731472, 2012.
 314.Steier J, Lunt A, Hart N, Polkey MI, Moxham J. Observational study of the effect of obesity on lung volumes. Thorax 69: 752‐759, 2014.
 315.Stenius‐Aarniala B, Poussa T, Kvarnstrom J, Gronlund EL, Ylikahri M, Mustajoki P. Immediate and long term effects of weight reduction in obese people with asthma: Randomised controlled study. BMJ 320: 827‐832, 2000.
 316.Sung HK, Doh KO, Son JE, Park JG, Bae Y, Choi S, Nelson SM, Cowling R, Nagy K, Michael IP, Koh GY, Adamson SL, Pawson T, Nagy A. Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metab 17: 61‐72, 2013.
 317.Sutherland TJ, Cowan JO, Young S, Goulding A, Grant AM, Williamson A, Brassett K, Herbison GP, Taylor DR. The association between obesity and asthma: Interactions between systemic and airway inflammation. Am J Respir Crit Care Med 178: 469‐475, 2008.
 318.Talukdar S, Oh DY, Bandyopadhyay G, Li D, Xu J, McNelis J, Lu M, Li P, Yan Q, Zhu Y, Ofrecio J, Lin M, Brenner MB, Olefsky JM. Neutrophils mediate insulin resistance in mice fed a high‐fat diet through secreted elastase. Nat Med 18: 1407‐1412, 2012.
 319.Tarantino G, Costantini S, Citro V, Conforti P, Capone F, Sorice A, Capone D. Interferon‐alpha 2 but not interferon‐gamma serum levels are associated with intramuscular fat in obese patients with nonalcoholic fatty liver disease. J Transl Med 17: 8, 2019.
 320.Tareen SHK, Kutmon M, Adriaens ME, Mariman ECM, de Kok TM, Arts ICW, Evelo CT. Exploring the cellular network of metabolic flexibility in the adipose tissue. Genes Nutr 13: 17, 2018.
 321.Tashiro H, Takahashi K, Sadamatsu H, Kato G, Kurata K, Kimura S, Sueoka‐Aragane N. Saturated fatty acid increases lung macrophages and augments house dust mite‐induced airway inflammation in mice fed with high‐fat diet. Inflammation 40: 1072‐1086, 2017.
 322.Taylor B, Mannino D, Brown C, Crocker D, Twum‐Baah N, Holguin F. Body mass index and asthma severity in the National Asthma Survey. Thorax 63: 14‐20, 2008.
 323.Terris DJ. Cosmetic enhancement associated with surgery for obstructive sleep apnea. Laryngoscope 109: 1045‐1050, 1999.
 324.Thompson CA, Eslick SR, Berthon BS, Wood LG. Asthma medication use in obese and healthy weight asthma: Systematic review/meta‐analysis. Eur Respir J 57: 2000612, 2021.
 325.Torriani M, Gill CM, Daley S, Oliveira AL, Azevedo DC, Bredella MA. Compartmental neck fat accumulation and its relation to cardiovascular risk and metabolic syndrome. Am J Clin Nutr 100: 1244‐1251, 2014.
 326.Trayhurn P, Wood IS. Adipokines: Inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 92: 347‐355, 2004.
 327.Trim W, Turner JE, Thompson D. Parallels in immunometabolic adipose tissue dysfunction with ageing and obesity. Front Immunol 9: 169, 2018.
 328.Tsuchiya T, Shimizu H, Horie T, Mori M. Expression of leptin receptor in lung: Leptin as a growth factor. Eur J Pharmacol 365: 273‐279, 1999.
 329.Tulbah AS, Pisano E, Scalia S, Young PM, Traini D, Ong HX. Inhaled simvastatin nanoparticles for inflammatory lung disease. Nanomedicine (Lond) 12: 2471‐2485, 2017.
 330.Turvey TA, Golden BA. Orbital anatomy for the surgeon. Oral Maxillofac Surg Clin North Am 24: 525‐536, 2012.
 331.Umlawska W. Adipose tissue content and distribution in children and adolescents with bronchial asthma. Respir Med 109: 200‐207, 2015.
 332.Unamuno X, Gomez‐Ambrosi J, Rodriguez A, Becerril S, Fruhbeck G, Catalan V. Adipokine dysregulation and adipose tissue inflammation in human obesity. Eur J Clin Investig 48: e12997, 2018.
 333.Unterborn J. Pulmonary function testing in obesity, pregnancy, and extremes of body habitus. Clin Chest Med 22: 759‐767, 2001.
 334.Valle A, Garcia‐Palmer FJ, Oliver J, Roca P. Sex differences in brown adipose tissue thermogenic features during caloric restriction. Cell Physiol Biochem 19: 195‐204, 2007.
 335.Van Harmelen V, Reynisdottir S, Eriksson P, Thorne A, Hoffstedt J, Lonnqvist F, Arner P. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 47: 913‐917, 1998.
 336.van Huisstede A, Rudolphus A, Castro Cabezas M, Biter LU, van de Geijn GJ, Taube C, Hiemstra PS, Braunstahl GJ. Effect of bariatric surgery on asthma control, lung function and bronchial and systemic inflammation in morbidly obese subjects with asthma. Thorax 70: 659‐667, 2015.
 337.Verboven K, Wouters K, Gaens K, Hansen D, Bijnen M, Wetzels S, Stehouwer CD, Goossens GH, Schalkwijk CG, Blaak EE, Jocken JW. Abdominal subcutaneous and visceral adipocyte size, lipolysis and inflammation relate to insulin resistance in male obese humans. Sci Rep 8: 4677, 2018.
 338.Villarroya J, Cereijo R, Gavalda‐Navarro A, Peyrou M, Giralt M, Villarroya F. New insights into the secretory functions of brown adipose tissue. J Endocrinol 243: R19‐R27, 2019.
 339.Vincent V, Thakkar H, Aggarwal S, Mridha AR, Ramakrishnan L, Singh A. ATP‐binding cassette transporter A1 (ABCA1) expression in adipose tissue and its modulation with insulin resistance in obesity. Diabetes Metab Syndr Obes 12: 275‐284, 2019.
 340.Votruba SB, Jensen MD. Sex‐specific differences in leg fat uptake are revealed with a high‐fat meal. Am J Physiol Endocrinol Metab 291: E1115‐E1123, 2006.
 341.Wajchenberg BL. Subcutaneous and visceral adipose tissue: Their relation to the metabolic syndrome. Endocr Rev 21: 697‐738, 2000.
 342.Wang KCW, Astell CJ, Wijesinghe P, Larcombe AN, Pinniger GJ, Zosky GR, Kennedy BF, Berry LJ, Sampson DD, James AL, Le Cras TD, Noble PB. Optical coherence tomography‐based contact indentation for diaphragm mechanics in a mouse model of transforming growth factor alpha induced lung disease. Sci Rep 7: 1517, 2017.
 343.Wang KCW, Donovan GM, Saglani S, Mauad T, James AL, Elliot JG, Noble PB. Growth of the airway smooth muscle layer from late gestation to childhood is mediated initially by hypertrophy and subsequently hyperplasia. Respirology 27: 493‐500, 2022.
 344.Wang KCW, Le Cras TD, Larcombe AN, Zosky GR, Elliot JG, James AL, Noble PB. Independent and combined effects of airway remodelling and allergy on airway responsiveness. Clin Sci (Lond) 132: 327‐338, 2018.
 345.Wang QA, Tao C, Gupta RK, Scherer PE. Tracking adipogenesis during white adipose tissue development, expansion and regeneration. Nat Med 19: 1338‐1344, 2013.
 346.Watson RA, Pride NB, Thomas EL, Fitzpatrick J, Durighel G, McCarthy J, Morin SX, Ind PW, Bell JD. Reduction of total lung capacity in obese men: Comparison of total intrathoracic and gas volumes. J Appl Physiol (1985) 108: 1605‐1612, 2010.
 347.Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112: 1796‐1808, 2003.
 348.Wenzel SE. Asthma: Defining of the persistent adult phenotypes. Lancet 368: 804‐813, 2006.
 349.Wenzel SE, Schwartz LB, Langmack EL, Halliday JL, Trudeau JB, Gibbs RL, Chu HW. Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics. Am J Resp Crit Care 160: 1001‐1008, 1999.
 350.WHO. Obesity and overweight [Factsheet], 2019. [01/08/2019, 2019]. https://www.who.int/news‐room/fact‐sheets/detail/obesity‐and‐overweight.
 351.WHO. Obesity, 2020 [11/02/2020, 2020]. https://www.who.int/health‐topics/obesity#tab=tab_1.
 352.WHO. Prevalence of obesity among adults. Global Health Observatory (GHO) Data: World Health Organisation, 2020. https://www.who.int/data/gho/data/indicators/indicator‐details/GHO/prevalence‐of‐obesity‐among‐adults‐bmi‐=‐30‐(age‐standardized‐estimate)‐(‐).
 353.WHO. Asthma, 2021 [17/07/2021, 2021]. https://www.who.int/news‐room/fact‐sheets/detail/asthma.
 354.Wilcox G. Insulin and insulin resistance. Clin Biochem Rev 26: 19‐39, 2005.
 355.Wilson JW, Li X, Pain MC. The lack of distensibility of asthmatic airways. Am Rev Respir Dis 148: 806‐809, 1993.
 356.Wong EH, Porter JD, Edwards MR, Johnston SL. The role of macrolides in asthma: Current evidence and future directions. Lancet Respir Med 2: 657‐670, 2014.
 357.Woo HJ, Yoo WJ, Bae CH, Song SY, Kim YW, Park SY, Kim YD. Leptin up‐regulates MUC5B expression in human airway epithelial cells via mitogen‐activated protein kinase pathway. Exp Lung Res 36: 262‐269, 2010.
 358.Woolcock AJ, Salome CM, Yan K. The shape of the dose‐response curve to histamine in asthmatic and normal subjects. Am Rev Respir Dis 130: 71‐75, 1984.
 359.Wu D, Molofsky AB, Liang HE, Ricardo‐Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332: 243‐247, 2011.
 360.Wu TD, Brigham EP, Keet CA, Brown TT, Hansel NN, McCormack MC. Association between prediabetes/diabetes and asthma exacerbations in a claims‐based obese asthma cohort. J Allergy Clin Immunol Pract 7: 1868‐1873 e1865, 2019.
 361.Yan H, Deshpande DA, Misior AM, Miles MC, Saxena H, Riemer EC, Pascual RM, Panettieri RA, Penn RB. Anti‐mitogenic effects of beta‐agonists and PGE2 on airway smooth muscle are PKA dependent. FASEB J 25: 389‐397, 2011.
 362.Yang W, Yang C, Luo J, Wei Y, Wang W, Zhong Y. Adiponectin promotes preadipocyte differentiation via the PPARgamma pathway. Mol Med Rep 17: 428‐435, 2018.
 363.Ye Z, Huang Y, Liu D, Chen X, Wang D, Huang D, Zhao L, Xiao X. Obesity induced by neonatal overfeeding worsens airway hyperresponsiveness and inflammation. PLoS One 7: e47013, 2012.
 364.Yeh YF, Huang SL. Enhancing effect of dietary cholesterol and inhibitory effect of pravastatin on allergic pulmonary inflammation. J Biomed Sci 11: 599‐606, 2004.
 365.Yoneshiro T, Aita S, Matsushita M, Okamatsu‐Ogura Y, Kameya T, Kawai Y, Miyagawa M, Tsujisaki M, Saito M. Age‐related decrease in cold‐activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring) 19: 1755‐1760, 2011.
 366.Yoo HJ, Choi KM. Adipokines as a novel link between obesity and atherosclerosis. World J Diabetes 5: 357‐363, 2014.
 367.Yoon J, Um HN, Jang J, Bae YA, Park WJ, Kim HJ, Yoon MS, Chung IY, Jung Y. Eosinophil activation by toll‐like receptor 4 ligands regulates macrophage polarization. Front Cell Dev Biol 7: 329, 2019.
 368.Zarkesh‐Esfahani H, Pockley AG, Wu Z, Hellewell PG, Weetman AP, Ross RJ. Leptin indirectly activates human neutrophils via induction of TNF‐alpha. J Immunol 172: 1809‐1814, 2004.
 369.Zelber‐Sagi S, Lotan R, Shlomai A, Webb M, Harrari G, Buch A, Nitzan Kaluski D, Halpern Z, Oren R. Predictors for incidence and remission of NAFLD in the general population during a seven‐year prospective follow‐up. J Hepatol 56: 1145‐1151, 2012.
 370.Zerah F, Harf A, Perlemuter L, Lorino H, Lorino AM, Atlan G. Effects of obesity on respiratory resistance. Chest 103: 1470‐1476, 1993.
 371.Zhang Y, Yang P, Cui R, Zhang M, Li H, Qian C, Sheng C, Qu S, Bu L. Eosinophils reduce chronic inflammation in adipose tissue by secreting Th2 cytokines and promoting M2 macrophages polarization. Int J Endocrinol 2015: 565760, 2015.
 372.Zhou H, Urso CJ, Jadeja V. Saturated fatty acids in obesity‐associated inflammation. J Inflamm Res 13: 1‐14, 2020.
 373.Zielinska‐Kazmierska B, Lewicki M, Manowska B. Madelung disease. Postepy Dermatol Alergol 32: 400‐403, 2015.
 374.Zwick RK, Guerrero‐Juarez CF, Horsley V, Plikus MV. Anatomical, physiological, and functional diversity of adipose tissue. Cell Metab 27: 68‐83, 2018.

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Article Title: From Beneath the Skin to the Airway Wall: Understanding the Pathological Role of Adipose Tissue in Comorbid Asthma‐Obesity
 

How to Cite

Carolyn J. Wang, Peter B. Noble, John G. Elliot, Alan L. James, Kimberley C. W. Wang. From Beneath the Skin to the Airway Wall: Understanding the Pathological Role of Adipose Tissue in Comorbid Asthma‐Obesity. Compr Physiol 2023, 13: 4321-4353. doi: 10.1002/cphy.c220011