Comprehensive Physiology Wiley Online Library

Contribution of Maladaptive Adipose Tissue Expansion to Development of Cardiovascular Disease

Full Article on Wiley Online Library



ABSTRACT

The overweight and obesity epidemic has led to an increase in the metabolic syndrome and associated cardiovascular disease (CVD). These abnormalities include insulin resistance, type 2 diabetes mellitus, vascular stiffness, hypertension, stroke, and coronary heart disease. Visceral white adipocyte tissue (WAT) expansion and associated fibrosis/stiffness of WAT promote insulin resistance and CVD through increases in proinflammatory adipokines, oxidative stress, activation of renin‐angiotensin‐aldosterone system, dysregulation of adipocyte apoptosis and autophagy, dysfunctional immune modulation, and adverse changes in the gut microbiome. The expansion of WAT is partly determined by activation of peroxisome proliferator‐activated receptor gamma and mammalian target of rapamycin/ribosomal S6 kinase signaling pathways. Further, the chronic activation of these signaling pathways may not only induce adipocyte hypertrophy and fibrosis, but also contribute to systemic inflammation, and impairment of insulin metabolic signaling in fat, liver, and skeletal muscle tissue. Therefore, the interplay of adipocyte dysfunction, maladaptive immune and inflammatory responses, and associated metabolic disorders often coexist leading to systemic low‐grade inflammation and insulin resistance that are associated with increased CVD in obese individuals. © 2017 American Physiological Society. Compr Physiol 7:253‐262, 2017.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1. Adipose tissue in the link of obesity and CVD. (A) Expansion of subcutaneous and VAT induces increases in oxidative stress, proinflammatory adipokines, activation of RAAS, dysregulation of adipocyte apoptosis and autophagy, and gut microbiota dysbiosis, resulting in insulin resistance, dyslipidemia, and associated CVD. (B) Interaction of ectopic adiposity and multiorgan dysregulation that is responsible for obesity and CVD. Nonalcoholic fatty liver disease is an important contributor in the obese individuals with CVD. RAAS, renin angiotensin‐aldosterone system; EC, endothelial cell; VSMC, vascular smooth muscle cell.


Figure 1. Adipose tissue in the link of obesity and CVD. (A) Expansion of subcutaneous and VAT induces increases in oxidative stress, proinflammatory adipokines, activation of RAAS, dysregulation of adipocyte apoptosis and autophagy, and gut microbiota dysbiosis, resulting in insulin resistance, dyslipidemia, and associated CVD. (B) Interaction of ectopic adiposity and multiorgan dysregulation that is responsible for obesity and CVD. Nonalcoholic fatty liver disease is an important contributor in the obese individuals with CVD. RAAS, renin angiotensin‐aldosterone system; EC, endothelial cell; VSMC, vascular smooth muscle cell.
References
 1. Alibasic E , Ramic E , Bajraktarevic A , Ljuca F , Batic‐Mujanovic O , and Zildzic M . Atherogenic dyslipidemia and residual vascular risk in practice of family doctor. Med Arch 69: 339‐341, 2015.
 2. Apostolopoulos V , de Courten MP , Stojanovska L , Blatch GL , Tangalakis K , and de Courten B . The complex immunological and inflammatory network of adipose tissue in obesity. Mol Nutr Food Res 60: 43‐57, 2016.
 3. Battaglia GM , Zheng D , Hickner RC , and Houmard JA . Effect of exercise training on metabolic flexibility in response to a high‐fat diet in obese individuals. Am J Physiol Endocrinol Metab 303: E1440‐E1445, 2012.
 4. Bays HE . Adiposopathy is “sick fat” a cardiovascular disease? J Am Coll Cardiol 57: 2461‐2473, 2011.
 5. Bostick B , Habibi J , Ma L , Aroor A , Rehmer N , Hayden MR , and Sowers JR . Dipeptidyl peptidase inhibition prevents diastolic dysfunction and reduces myocardial fibrosis in a mouse model of Western diet induced obesity. Metabolism 63: 1000‐1011, 2014.
 6. Boyer F , Diotel N , Girard D , Rondeau P , Essop MF , and Bourdon E . Enhanced oxidative stress in adipose tissue from diabetic mice, possible contribution of glycated albumin. Biochem Biophys Res Commun 473: 154‐160, 2016.
 7. Castro JP , El‐Atat FA , McFarlane SI , Aneja A , and Sowers JR . Cardiometabolic syndrome: pathophysiology and treatment. Curr Hypertens Rep 5: 393‐401, 2003.
 8. Catalan V , Gomez‐Ambrosi J , Rodriguez A , Ramirez B , Andrada P , Rotellar F , Valenti V , Moncada R , Marti P , Silva C , Salvador J , and Fruhbeck G . Expression of S6K1 in human visceral adipose tissue is upregulated in obesity and related to insulin resistance and inflammation. Acta Diabetol 52: 257‐266, 2015.
 9. Chatterjee S , Ganini D , Tokar EJ , Kumar A , Das S , Corbett J , Kadiiska MB , Waalkes MP , Diehl AM , and Mason RP . Leptin is key to peroxynitrite‐mediated oxidative stress and Kupffer cell activation in experimental non‐alcoholic steatohepatitis. J Hepatol 58: 778‐784, 2013.
 10. Chouchani ET , Kazak L , Jedrychowski MP , Lu GZ , Erickson BK , Szpyt J , Pierce KA , Laznik‐Bogoslavski D , Vetrivelan R , Clish CB , Robinson AJ , Gygi SP , and Spiegelman BM . Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1. Nature 532: 112‐116, 2016.
 11. Constantin‐Teodosiu D , Constantin D , Stephens F , Laithwaite D , and Greenhaff PL . The role of FOXO and PPAR transcription factors in diet‐mediated inhibition of PDC activation and carbohydrate oxidation during exercise in humans and the role of pharmacological activation of PDC in overriding these changes. Diabetes 61: 1017‐1024, 2012.
 12. Corpeleijn E , Saris WH , and Blaak EE . Metabolic flexibility in the development of insulin resistance and type 2 diabetes: Effects of lifestyle. Obes Rev 10: 178‐193, 2009.
 13. Curtis JP , Selter JG , Wang Y , Rathore SS , Jovin IS , Jadbabaie F , Kosiborod M , Portnay EL , Sokol SI , Bader F , and Krumholz HM . The obesity paradox: Body mass index and outcomes in patients with heart failure. Arch Intern Med 165: 55‐61, 2005.
 14. DeMarco VG , Aroor AR , and Sowers JR . The pathophysiology of hypertension in patients with obesity. Nat Rev Endocrinol 10: 364‐376, 2014.
 15. DeMarco VG , Habibi J , Jia G , Aroor AR , Ramirez‐Perez FI , Martinez‐Lemus LA , Bender SB , Garro M , Hayden MR , Sun Z , Meininger GA , Manrique C , Whaley‐Connell A , and Sowers JR . Low‐dose mineralocorticoid receptor blockade prevents Western diet‐induced arterial stiffening in female mice. Hypertension 66: 99‐107, 2015.
 16. Dozio E , Malavazos AE , Vianello E , Briganti S , Dogliotti G , Bandera F , Giacomazzi F , Castelvecchio S , Menicanti L , Sigruener A , Schmitz G , and Corsi Romanelli MM . Interleukin‐15 and soluble interleukin‐15 receptor alpha in coronary artery disease patients: Association with epicardial fat and indices of adipose tissue distribution. PLoS One 9: e90960, 2014.
 17. Fasshauer M , and Bluher M . Adipokines in health and disease. Trends Pharmacol Sci 36: 461‐470, 2015.
 18. Feraco A , Armani A , Mammi C , Fabbri A , Rosano GM , and Caprio M . Role of mineralocorticoid receptor and renin‐angiotensin‐aldosterone system in adipocyte dysfunction and obesity. J Steroid Biochem Mol Biol 137: 99‐106, 2013.
 19. Fitzgibbons TP , and Czech MP . Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: Basic mechanisms and clinical associations. J Am Heart Assoc 3: e000582, 2014.
 20. Fujisaka S , Usui I , Bukhari A , Ikutani M , Oya T , Kanatani Y , Tsuneyama K , Nagai Y , Takatsu K , Urakaze M , Kobayashi M , and Tobe K . Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet‐induced obese mice. Diabetes 58: 2574‐2582, 2009.
 21. Gardner CD , Offringa LC , Hartle JC , Kapphahn K , and Cherin R . Weight loss on low‐fat vs. low‐carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial. Obesity (Silver Spring) 24: 79‐86, 2016.
 22. Geurts L , Lazarevic V , Derrien M , Everard A , Van Roye M , Knauf C , Valet P , Girard M , Muccioli GG , Francois P , de Vos WM , Schrenzel J , Delzenne NM , and Cani PD . Altered gut microbiota and endocannabinoid system tone in obese and diabetic leptin‐resistant mice: Impact on apelin regulation in adipose tissue. Front Microbiol 2: 149, 2011.
 23. Gil‐Ortega M , Somoza B , Huang Y , Gollasch M , and Fernandez‐Alfonso MS . Regional differences in perivascular adipose tissue impacting vascular homeostasis. Trends Endocrinol Metab 26: 367‐375, 2015.
 24. Gil A , Olza J , Gil‐Campos M , Gomez‐Llorente C , and Aguilera CM . Is adipose tissue metabolically different at different sites? Int J Pediatr Obes 6(Suppl 1): 13‐20, 2011.
 25. Godo S , Sawada A , Saito H , Ikeda S , Enkhjargal B , Suzuki K , Tanaka S , and Shimokawa H . Disruption of physiological balance between nitric oxide and endothelium‐dependent hyperpolarization impairs cardiovascular homeostasis in mice. Arterioscler Thromb Vasc Biol 36: 97‐107, 2016.
 26. Hainer V , and Aldhoon‐Hainerova I . Obesity paradox does exist. Diabetes Care 36(Suppl 2): S276‐S281, 2013.
 27. Haissaguerre M , Saucisse N , and Cota D . Influence of mTOR in energy and metabolic homeostasis. Mol Cell Endocrinol 397: 67‐77, 2014.
 28. Hajsadeghi F , Nabavi V , Bhandari A , Choi A , Vincent H , Flores F , Budoff M , and Ahmadi N . Increased epicardial adipose tissue is associated with coronary artery disease and major adverse cardiovascular events. Atherosclerosis 237: 486‐489, 2014.
 29. Hassan M , Latif N , and Yacoub M . Adipose tissue: Friend or foe? Nat Rev Cardiol 9: 689‐702, 2012.
 30. Hell MM , Ding X , Rubeaux M , Slomka P , Gransar H , Terzopoulos D , Hayes S , Marwan M , Achenbach S , Berman DS , and Dey D . Epicardial adipose tissue volume but not density is an independent predictor for myocardial ischemia. J Cardiovasc Comput Tomogr 10: 141‐149, 2016.
 31. Huby AC , Antonova G , Groenendyk J , Gomez‐Sanchez CE , Bollag WB , Filosa JA , and Belin de Chantemele EJ . Adipocyte‐derived hormone leptin is a direct regulator of aldosterone secretion, which promotes endothelial dysfunction and cardiac fibrosis. Circulation 132: 2134‐2145, 2015.
 32. Huot ME , Vogel G , Zabarauskas A , Ngo CT , Coulombe‐Huntington J , Majewski J , and Richard S . The Sam68 STAR RNA‐binding protein regulates mTOR alternative splicing during adipogenesis. Mol Cell 46: 187‐199, 2012.
 33. Iacobellis G . Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol 11: 363‐371, 2015.
 34. Iacobellis G . Epicardial fat: A new cardiovascular therapeutic target. Curr Opin Pharmacol 27: 13‐18, 2016.
 35. Inzucchi SE , Zinman B , Wanner C , Ferrari R , Fitchett D , Hantel S , Espadero RM , Woerle HJ , Broedl UC , and Johansen OE . SGLT‐2 inhibitors and cardiovascular risk: Proposed pathways and review of ongoing outcome trials. Diab Vasc Dis Res 12: 90‐100, 2015.
 36. Jia G , Aroor AR , Martinez‐Lemus LA , and Sowers JR . Overnutrition, mTOR signaling, and cardiovascular diseases. Am J Physiol Regul Integr Comp Physiol 307: R1198‐R1206, 2014.
 37. Jia G , Habibi J , Aroor AR , Martinez‐Lemus LA , DeMarco VG , Ramirez‐Perez FI , Sun Z , Hayden MR , Meininger GA , Mueller KB , Jaffe IZ , and Sowers JR . Endothelial mineralocorticoid receptor mediates diet‐induced aortic stiffness in females. Circ Res 118: 935‐943, 2016.
 38. Jia G , Habibi J , Bostick BP , Ma L , DeMarco VG , Aroor AR , Hayden MR , Whaley‐Connell AT , and Sowers JR . Uric acid promotes left ventricular diastolic dysfunction in mice fed a Western diet. Hypertension 65: 531‐539, 2015.
 39. Jia G , Habibi J , DeMarco VG , Martinez‐Lemus LA , Ma L , Whaley‐Connell AT , Aroor AR , Domeier TL , Zhu Y , Meininger GA , Barrett Mueller K , Jaffe IZ , and Sowers JR . Endothelial mineralocorticoid receptor deletion prevents diet‐induced cardiac diastolic dysfunction in females. Hypertension 66: 1159‐1167, 2015.
 40. Jia G , and Sowers JR . Autophagy: A housekeeper in cardiorenal metabolic health and disease. Biochim Biophys Acta 1852: 219‐224, 2015.
 41. Jindal A , Whaley‐Connell A , and Sowers JR . Obesity and heart failure as a mediator of the cerebrorenal interaction. Contrib Nephrol 179: 15‐23, 2013.
 42. Kandadi MR , Panzhinskiy E , Roe ND , Nair S , Hu D , and Sun A . Deletion of protein tyrosine phosphatase 1B rescues against myocardial anomalies in high fat diet‐induced obesity: Role of AMPK‐dependent autophagy. Biochim Biophys Acta 1852: 299‐309, 2015.
 43. 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 , and 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.
 44. Karpe F , and Pinnick KE . Biology of upper‐body and lower‐body adipose tissue–link to whole‐body phenotypes. Nat Rev Endocrinol 11: 90‐100, 2015.
 45. Kenchaiah S , Evans JC , Levy D , Wilson PW , Benjamin EJ , Larson MG , Kannel WB , and Vasan RS . Obesity and the risk of heart failure. N Engl J Med 347: 305‐313, 2002.
 46. Khaidakov M , Mitra S , Kang BY , Wang X , Kadlubar S , Novelli G , Raj V , Winters M , Carter WC , and Mehta JL . Oxidized LDL receptor 1 (OLR1) as a possible link between obesity, dyslipidemia and cancer. PLoS One 6: e20277, 2011.
 47. Kim JA , Jang HJ , Martinez‐Lemus LA , and Sowers JR . Activation of mTOR/p70S6 kinase by ANG II inhibits insulin‐stimulated endothelial nitric oxide synthase and vasodilation. Am J Physiol Endocrinol Metab 302: E201‐208, 2012.
 48. Kobuchi S , Miura K , Iwao H , and Ayajiki K . Nitric oxide modulation of endothelium‐derived hyperpolarizing factor in agonist‐induced depressor responses in anesthetized rats. Eur J Pharmacol 762: 26‐34, 2015.
 49. Kovacova Z , Tharp WG , Liu D , Wei W , Xie H , Collins S , and Pratley RE . Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes. Obesity (Silver Spring) 24: 820‐828, 2016.
 50. Lang F , and Stournaras C . Serum and glucocorticoid inducible kinase, metabolic syndrome, inflammation, and tumor growth. Hormones (Athens) 12: 160‐171, 2013.
 51. Lauer MS , Anderson KM , Kannel WB , and Levy D . The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study. JAMA 266: 231‐236, 1991.
 52. Lavie CJ , Osman AF , Milani RV , and Mehra MR . Body composition and prognosis in chronic systolic heart failure: The obesity paradox. Am J Cardiol 91: 891‐894, 2003.
 53. Lee MJ , Wu Y , and Fried SK . Adipose tissue heterogeneity: Implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med 34: 1‐11, 2013.
 54. Lee YH , Mottillo EP , and Granneman JG . Adipose tissue plasticity from WAT to BAT and in between. Biochim Biophys Acta 1842: 358‐369, 2014.
 55. Lehman SJ , Massaro JM , Schlett CL , O'Donnell CJ , Hoffmann U , and Fox CS . Peri‐aortic fat, cardiovascular disease risk factors, and aortic calcification: The Framingham Heart Study. Atherosclerosis 210: 656‐661, 2010.
 56. Ley RE , Backhed F , Turnbaugh P , Lozupone CA , Knight RD , and Gordon JI . Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 102: 11070‐11075, 2005.
 57. Lim S , and Meigs JB . Ectopic fat and cardiometabolic and vascular risk. Int J Cardiol 169: 166‐176, 2013.
 58. Lim S , and Meigs JB . Links between ectopic fat and vascular disease in humans. Arterioscler Thromb Vasc Biol 34: 1820‐1826, 2014.
 59. Liu K , Zhao E , Ilyas G , Lalazar G , Lin Y , Haseeb M , Tanaka KE , and Czaja MJ . Impaired macrophage autophagy increases the immune response in obese mice by promoting proinflammatory macrophage polarization. Autophagy 11: 271‐284, 2015.
 60. Liu R , Pulliam DA , Liu Y , and Salmon AB . Dynamic differences in oxidative stress and the regulation of metabolism with age in visceral versus subcutaneous adipose. Redox Biol 6: 401‐408, 2015.
 61. Liu Y , Aron‐Wisnewsky J , Marcelin G , Genser L , Le Naour G , Torcivia A , Bauvois B , Bouchet S , Pelloux V , Sasso M , Miette V , Tordjman J , and Clement K . Accumulation and changes in composition of collagens in subcutaneous adipose tissue after bariatric surgery. J Clin Endocrinol Metab 101: 293‐304, 2016.
 62. Luna‐Luna M , Medina‐Urrutia A , Vargas‐Alarcon G , Coss‐Rovirosa F , Vargas‐Barron J , and Perez‐Mendez O . Adipose tissue in metabolic syndrome: Onset and progression of atherosclerosis. Arch Med Res 46: 392‐407, 2015.
 63. Mahana D , Trent CM , Kurtz ZD , Bokulich NA , Battaglia T , Chung J , Muller CL , Li H , Bonneau RA , and Blaser MJ . Antibiotic perturbation of the murine gut microbiome enhances the adiposity, insulin resistance, and liver disease associated with high‐fat diet. Genome Med 8: 48, 2016.
 64. Mentzel CM , Anthon C , Jacobsen MJ , Karlskov‐Mortensen P , Bruun CS , Jorgensen CB , Gorodkin J , Cirera S , and Fredholm M . Gender and obesity specific MicroRNA expression in adipose tissue from lean and obese pigs. PLoS One 10: e0131650, 2015.
 65. Muller‐Wieland D , Knebel B , Haas J , and Kotzka J . [SREBP‐1 and fatty liver. Clinical relevance for diabetes, obesity, dyslipidemia and atherosclerosis]. Herz 37: 273‐278, 2012.
 66. Noyes AM , Dua K , Devadoss R , and Chhabra L . Cardiac adipose tissue and its relationship to diabetes mellitus and cardiovascular disease. World J Diabetes 5: 868‐876, 2014.
 67. Nunez R , Sancho‐Martinez SM , Novoa JM , and Lopez‐Hernandez FJ . Apoptotic volume decrease as a geometric determinant for cell dismantling into apoptotic bodies. Cell Death Differ 17: 1665‐1671, 2010.
 68. Nyman E , Rajan MR , Fagerholm S , Brannmark C , Cedersund G , and Stralfors P . A single mechanism can explain network‐wide insulin resistance in adipocytes from obese patients with type 2 diabetes. J Biol Chem 289: 33215‐33230, 2014.
 69. O'Brien EC , and Thomas LE . Untangling the paradox: Obesity as prognostic marker in prevalent cardiovascular disease. Am Heart J 172: 170‐172, 2016.
 70. Omar A , Chatterjee TK , Tang Y , Hui DY , and Weintraub NL . Proinflammatory phenotype of perivascular adipocytes. Arterioscler Thromb Vasc Biol 34: 1631‐1636, 2014.
 71. Oue K , Zhang J , Harada‐Hada K , Asano S , Yamawaki Y , Hayashiuchi M , Furusho H , Takata T , Irifune M , Hirata M , and Kanematsu T . Phospholipase C‐related catalytically inactive protein is a new modulator of thermogenesis promoted by beta‐adrenergic receptors in brown adipocytes. J Biol Chem 291: 4185‐4196, 2016.
 72. Ozen G , Daci A , Norel X , and Topal G . Human perivascular adipose tissue dysfunction as a cause of vascular disease: Focus on vascular tone and wall remodeling. Eur J Pharmacol 766: 16‐24, 2015.
 73. Pellegrinelli V , Carobbio S , and Vidal‐Puig A . Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues. Diabetologia 59: 1075‐1088, 2016.
 74. Ridaura VK , Faith JJ , Rey FE , Cheng J , Duncan AE , Kau AL , Griffin NW , Lombard V , Henrissat B , Bain JR , Muehlbauer MJ , Ilkayeva O , Semenkovich CF , Funai K , Hayashi DK , Lyle BJ , Martini MC , Ursell LK , Clemente JC , Van Treuren W , Walters WA , Knight R , Newgard CB , Heath AC , and Gordon JI . Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341: 1241214, 2013.
 75. Rodriguez A , Ezquerro S , Mendez‐Gimenez L , Becerril S , and Fruhbeck G . Revisiting the adipocyte: A model for integration of cytokine signaling in the regulation of energy metabolism. Am J Physiol Endocrinol Metab 309: E691‐E714, 2015.
 76. Russo I , Del Mese P , Doronzo G , Mattiello L , Viretto M , Bosia A , Anfossi G , and Trovati M . Resistance to the nitric oxide/cyclic guanosine 5′‐monophosphate/protein kinase G pathway in vascular smooth muscle cells from the obese Zucker rat, a classical animal model of insulin resistance: Role of oxidative stress. Endocrinology 149: 1480‐1489, 2008.
 77. Sacca L , and Napoli R . Insulin resistance in chronic heart failure: A difficult bull to take by the horns. Nutr Metab Cardiovasc Dis 19: 303‐305, 2009.
 78. Sam S , Haffner S , Davidson MH , D'Agostino RB, Sr. , Feinstein S , Kondos G , Perez A , and Mazzone T . Relationship of abdominal visceral and subcutaneous adipose tissue with lipoprotein particle number and size in type 2 diabetes. Diabetes 57: 2022‐2027, 2008.
 79. Schlessinger K , Li W , Tan Y , Liu F , Souza SC , Tozzo E , Liu K , Thompson JR , Wang L , and Muise ES . Gene expression in WAT from healthy humans and monkeys correlates with FGF21‐induced browning of WAT in mice. Obesity (Silver Spring) 23: 1818‐1829, 2015.
 80. Schrauwen‐Hinderling VB , Hesselink MK , Meex R , van der Made S , Schar M , Lamb H , Wildberger JE , Glatz J , Snoep G , Kooi ME , and Schrauwen P . Improved ejection fraction after exercise training in obesity is accompanied by reduced cardiac lipid content. J Clin Endocrinol Metab 95: 1932‐1938, 2010.
 81. Schrauwen‐Hinderling VB , Meex RC , Hesselink MK , van de Weijer T , Leiner T , Schar M , Lamb HJ , Wildberger JE , Glatz JF , Schrauwen P , and Kooi ME . Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction. Cardiovasc Diabetol 10: 47, 2011.
 82. Selcuk A , Bulucu F , Kalafat F , Cakar M , Demirbas S , Karaman M , Ay SA , Saglam K , Balta S , Demirkol S , and Arslan E . Skinfold thickness as a predictor of arterial stiffness: Obesity and fatness linked to higher stiffness measurements in hypertensive patients. Clin Exp Hypertens 35: 459‐464, 2013.
 83. Shen J , Obin MS , and Zhao L . The gut microbiota, obesity and insulin resistance. Mol Aspects Med 34: 39‐58, 2013.
 84. Shen W , Wang Z , Punyanita M , Lei J , Sinav A , Kral JG , Imielinska C , Ross R , and Heymsfield SB . Adipose tissue quantification by imaging methods: A proposed classification. Obes Res 11: 5‐16, 2003.
 85. Sole M , Hernandez‐Guillamon M , Boada M , and Unzeta M . p53 phosphorylation is involved in vascular cell death induced by the catalytic activity of membrane‐bound SSAO/VAP‐1. Biochim Biophys Acta 1783: 1085‐1094, 2008.
 86. Srinivasa S , Fitch KV , Wong K , Torriani M , Mayhew C , Stanley T , Lo J , Adler GK , and Grinspoon SK . RAAS activation is associated with visceral adiposity and insulin resistance among HIV‐infected patients. J Clin Endocrinol Metab 100: 2873‐2882, 2015.
 87. Talman AH , Psaltis PJ , Cameron JD , Meredith IT , Seneviratne SK , and Wong DT . Epicardial adipose tissue: Far more than a fat depot. Cardiovasc Diagn Ther 4: 416‐429, 2014.
 88. Taube M , Andersson‐Assarsson JC , Lindberg K , Pereira MJ , Gabel M , Svensson MK , Eriksson JW , and Svensson PA . Evaluation of reference genes for gene expression studies in human brown adipose tissue. Adipocyte 4: 280‐285, 2015.
 89. Thethi T , Kamiyama M , and Kobori H . The link between the renin‐angiotensin‐aldosterone system and renal injury in obesity and the metabolic syndrome. Curr Hypertens Rep 14: 160‐169, 2012.
 90. Toro AR , Maymo JL , Ibarbalz FM , Perez‐Perez A , Maskin B , Faletti AG , Sanchez‐Margalet V , and Varone CL . Leptin is an anti‐apoptotic effector in placental cells involving p53 downregulation. PLoS One 9: e99187, 2014.
 91. Turnbaugh PJ , Ley RE , Mahowald MA , Magrini V , Mardis ER , and Gordon JI . An obesity‐associated gut microbiome with increased capacity for energy harvest. Nature 444: 1027‐1031, 2006.
 92. Vincent MA , Clerk LH , Lindner JR , Klibanov AL , Clark MG , Rattigan S , and Barrett EJ . Microvascular recruitment is an early insulin effect that regulates skeletal muscle glucose uptake in vivo. Diabetes 53: 1418‐1423, 2004.
 93. von Bibra H , and St John Sutton M . Impact of diabetes on postinfarction heart failure and left ventricular remodeling. Curr Heart Fail Rep 8: 242‐251, 2011.
 94. Wang X , Wang J , Luo H , Chen C , Pei F , Cai Y , Yang X , Wang N , Fu J , Xu Z , Zhou L , and Zeng C . Prenatal lipopolysaccharide exposure causes mesenteric vascular dysfunction through the nitric oxide and cyclic guanosine monophosphate pathway in offspring. Free Radic Biol Med 86: 322‐330, 2015.
 95. White UA , Fitch MD , Beyl RA , Hellerstein MK , and Ravussin E . Differences in in vivo cellular kinetics in abdominal and femoral subcutaneous adipose tissue in women. Diabetes 65: 1642‐1647, 2016.
 96. Wong AK , Symon R , AlZadjali MA , Ang DS , Ogston S , Choy A , Petrie JR , Struthers AD , and Lang CC . The effect of metformin on insulin resistance and exercise parameters in patients with heart failure. Eur J Heart Fail 14: 1303‐1310, 2012.
 97. Xia N , Horke S , Habermeier A , Closs EI , Reifenberg G , Gericke A , Mikhed Y , Munzel T , Daiber A , Forstermann U , and Li H . Uncoupling of endothelial nitric oxide synthase in perivascular adipose tissue of diet‐induced obese mice. Arterioscler Thromb Vasc Biol 36: 78‐85, 2016.
 98. Yamaguchi R , Yamamoto T , Sakamoto A , Ishimaru Y , Narahara S , Sugiuchi H , and Yamaguchi Y . Chemokine profiles of human visceral adipocytes from cryopreserved preadipocytes: Neutrophil activation and induction of nuclear factor‐kappa B repressing factor. Life Sci 143: 225‐230, 2015.
 99. Yoon MS , Zhang C , Sun Y , Schoenherr CJ , and Chen J . Mechanistic target of rapamycin controls homeostasis of adipogenesis. J Lipid Res 54: 2166‐2173, 2013.
 100. Yuan X , Zhang L , Wang S , Ou Y , Wang Q , Peng W , Luo H , Cheng Z , and Zhu X . Mitochondrial apoptosis and autophagy in the process of adipose‐derived stromal cell differentiation into astrocytes. Cell Biol Int 40: 156‐165, 2016.
 101. Zhang W , Hartmann R , Tun HM , Elson CO , Khafipour E , and Garvey WT . Deletion of the toll‐like receptor 5 gene per se does not determine the gut microbiome profile that induces metabolic syndrome: Environment trumps genotype. PLoS One 11: e0150943, 2016.
 102. Zhou J , Wang Q , Ding Y , and Zou MH . Hypochlorous acid via peroxynitrite activates protein kinase Ctheta and insulin resistance in adipocytes. J Mol Endocrinol 54: 25‐37, 2015.
 103. Zhou J , Xu G , Ma S , Li F , Yuan M , Xu H , and Huang K . Catalpol ameliorates high‐fat diet‐induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF‐kappaB pathways. Biochem Biophys Res Commun 467: 853‐858, 2015.
 104. Zinman B , Wanner C , Lachin JM , Fitchett D , Bluhmki E , Hantel S , Mattheus M , Devins T , Johansen OE , Woerle HJ , Broedl UC , Inzucchi SE , and Investigators E‐RO . Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373: 2117‐2128, 2015.

Related Articles:

Adiposity
Adipose tissue in diabetes
Diabetes and Obesity
Immunity and Inflammation
Systemic Hypertension

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Guanghong Jia, Yan Jia, James R. Sowers. Contribution of Maladaptive Adipose Tissue Expansion to Development of Cardiovascular Disease. Compr Physiol 2016, 7: 253-262. doi: 10.1002/cphy.c160014