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Adipose Tissue‐Derived Omentin‐1 Function and Regulation

Takuya Watanabe, Kaho Watanabe‐Kominato, Yui Takahashi, Miho Kojima, Rena Watanabe

10.1002/cphy.c160043

Source: Volume 7, Issue 3, July 2017

Published online: June 2017

Full Article on Wiley Online Library



ABSTRACT

Omentin‐1, also known as intelectin‐1, is a recently identified novel adipocytokine of 313 amino acids, which is expressed in visceral (omental and epicardial) fat as well as mesothelial cells, vascular cells, airway goblet cells, small intestine, colon, ovary, and plasma. The level of omentin‐1 expression in (pre)adipocytes is decreased by glucose/insulin and stimulated by fibroblast growth factor‐21 and dexamethasone. Several lines of experimental evidence have shown that omentin‐1 plays crucial roles in the maintenance of body metabolism and insulin sensitivity, and has anti‐inflammatory, anti‐atherosclerotic, and cardiovascular protective effects via AMP‐activated protein kinase/Akt/nuclear factor‐κB/mitogen‐activated protein kinase (ERK, JNK, and p38) signaling. Clinical studies have indicated the usage of circulating omentin‐1 as a biomarker of obesity, metabolic disorders including insulin resistance, diabetes, and metabolic syndrome, and atherosclerotic cardiovascular diseases. It is also possible to use circulating omentin‐1 as a biomarker of bone metabolism, inflammatory diseases, cancers, sleep apnea syndrome, preeclampsia, and polycystic ovary syndrome. Decreased omentin‐1 levels are generally associated with these diseases. However, omentin‐1 increases to counteract the acute phase after onset of these diseases. These findings indicate that omentin‐1 may be a negative risk factor for these diseases, and also act as an acute‐phase reactant by its anti‐inflammatory and atheroprotective effects. Therapeutic strategies to restore omentin‐1 levels may be valuable for the prevention or treatment of these diseases. Weight loss, olive oil‐rich diet, aerobic training, and treatment with atorvastatin and antidiabetic drugs (metformin, pioglitazone, and exenatide) are effective means of increasing circulating omentin‐1 levels. This review provides insights into the potential use of omentin‐1 as a biomarker and therapeutic target for these diseases. © 2017 American Physiological Society. Compr Physiol 7:765‐781, 2017.

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Figure 1. Figure 1. Favorable and unfavorable effects of novel adipocytokines on energy homeostasis, glucose metabolism, cardiovascular system, inflammation, and oxidative stress. Adiponectin, omentin‐1, vaspin, chemerin, resistin, and leptin are selected as novel adipocytokines. (+) indicates favorable effect and (−) indicates unfavorable effect on energy homeostasis, glucose metabolism, cardiovascular protection, anti‐inflammation response, and antioxidative stress.
Figure 2. Figure 2. Genomic structure of human omentin gene. (A) The genomic structure of the human omentin (intelectin) gene. (B) The exon‐intron junctions. Exons are indicated as square boxes and the open reading frame is indicated as black regions. The sequences and numbers of exon junctions are shown earlier the square boxes. The consensus sequences for splicing are underlined. The usage of this figure from the original paper (131) is permitted by the American Society for Biochemistry and Molecular Biology.
Figure 3. Figure 3. Comparison of amino acid sequences between human omentin‐1 and mouse omentin‐1. This figure illustrates the alignment of amino acid sequences of human omentin‐1 (GenBank AAS49907; intelectin‐1, BAA96094) and mouse omentin‐1 (intelectin‐1, BAA31992). The homologous amino acids are shown in outline characters on black backgrounds, which are 81.5% identical (255/313 amino acids). The usage of this figure from the original paper (132) is permitted by the Oxford University Press.
Figure 4. Figure 4. Comparison of amino acid sequence between human omentin‐1 and human omentin‐2. This figure illustrates the alignment of amino acid sequences of human omentin‐1 (GenBank AAS49907; intelectin‐1, BAA96094) and human omentin‐2 (intelectin‐2, EAW52685). The homologous amino acids are shown in outline characters on black backgrounds, which are 83.0% identical (264/318 amino acids). Alignment of amino acid sequences between human omentin‐1 and human omentin‐2 is from Basic Local Alignment Search Tool.
Figure 5. Figure 5. Expression of human omentin‐1 in human vascular cells. Aliquots of protein extracts (50 μg) derived from human monocytes, HMDMs, HUVECs, and HASMCs were separated by 10% sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and then immunoblotted with antibodies against human omentin‐1 (upper). α‐Tubulin served as a loading control (beneath). Molecular size is expressed in kilodaltons (kDa).
Figure 6. Figure 6. Mechanisms underlying the atheroprotective effects of omentin‐1. This figure illustrates the suppressive effects of omentin‐1 on atherogenesis in the arterial wall. Omentin‐1 prevents atherosclerosis by suppressing the inflammatory responses in endothelial cells (ECs), the adhesion of monocytes (Mo) to ECs, oxidized low‐density lipoprotein (LDL)‐induced foam cell formation in Mo‐derived macrophages (Mφ), the migration and proliferation of vascular smooth muscle cells (VSMCs), and the production of extracellular matrix (ECM), such as collagen‐1 and collagen‐3, by VSMCs. Abbreviations: ACAT‐1, acyl‐coenzyme A:cholesterol acyltransferase‐1; ABCA1, ATP‐binding cassette transporter A1; DM, diabetes mellitus; HT, hypertension, ICAM‐1, intercellular adhesion molecule‐1; M‐CSF, macrophage colony‐stimulating factor; NO, nitric oxide; VCAM‐1, vascular adhesion molecule‐1.
Figure 7. Figure 7. Expression of human omentin‐1 in epicardial adipose tissue. These pictures (Alexa Fluor 488 confocal images) show fluorescent immunohistochemistry staining of human omentin‐1 (green) in epicardial adipose tissues in CAD and non‐CAD patients.
Figure 8. Figure 8. Intracellular signaling pathways for multiple beneficial effects of omentin‐1. This figure illustrates the secretion source, intracellular signals, and main beneficial effects of omentin‐1. Abbreviations: AMPK, AMP‐activated protein kinase; eNOS, endothelial nitric oxide synthase; ERK, extracellular signal‐regulated kinase; JNK, c‐Jun N‐terminal kinase; MAPK, mitogen‐activated protein kinase; NF‐κB, nuclear factor‐κB; PI3K, phosphoinositide 3‐kinase.


Figure 1. Favorable and unfavorable effects of novel adipocytokines on energy homeostasis, glucose metabolism, cardiovascular system, inflammation, and oxidative stress. Adiponectin, omentin‐1, vaspin, chemerin, resistin, and leptin are selected as novel adipocytokines. (+) indicates favorable effect and (−) indicates unfavorable effect on energy homeostasis, glucose metabolism, cardiovascular protection, anti‐inflammation response, and antioxidative stress.


Figure 2. Genomic structure of human omentin gene. (A) The genomic structure of the human omentin (intelectin) gene. (B) The exon‐intron junctions. Exons are indicated as square boxes and the open reading frame is indicated as black regions. The sequences and numbers of exon junctions are shown earlier the square boxes. The consensus sequences for splicing are underlined. The usage of this figure from the original paper (131) is permitted by the American Society for Biochemistry and Molecular Biology.


Figure 3. Comparison of amino acid sequences between human omentin‐1 and mouse omentin‐1. This figure illustrates the alignment of amino acid sequences of human omentin‐1 (GenBank AAS49907; intelectin‐1, BAA96094) and mouse omentin‐1 (intelectin‐1, BAA31992). The homologous amino acids are shown in outline characters on black backgrounds, which are 81.5% identical (255/313 amino acids). The usage of this figure from the original paper (132) is permitted by the Oxford University Press.


Figure 4. Comparison of amino acid sequence between human omentin‐1 and human omentin‐2. This figure illustrates the alignment of amino acid sequences of human omentin‐1 (GenBank AAS49907; intelectin‐1, BAA96094) and human omentin‐2 (intelectin‐2, EAW52685). The homologous amino acids are shown in outline characters on black backgrounds, which are 83.0% identical (264/318 amino acids). Alignment of amino acid sequences between human omentin‐1 and human omentin‐2 is from Basic Local Alignment Search Tool.


Figure 5. Expression of human omentin‐1 in human vascular cells. Aliquots of protein extracts (50 μg) derived from human monocytes, HMDMs, HUVECs, and HASMCs were separated by 10% sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and then immunoblotted with antibodies against human omentin‐1 (upper). α‐Tubulin served as a loading control (beneath). Molecular size is expressed in kilodaltons (kDa).


Figure 6. Mechanisms underlying the atheroprotective effects of omentin‐1. This figure illustrates the suppressive effects of omentin‐1 on atherogenesis in the arterial wall. Omentin‐1 prevents atherosclerosis by suppressing the inflammatory responses in endothelial cells (ECs), the adhesion of monocytes (Mo) to ECs, oxidized low‐density lipoprotein (LDL)‐induced foam cell formation in Mo‐derived macrophages (Mφ), the migration and proliferation of vascular smooth muscle cells (VSMCs), and the production of extracellular matrix (ECM), such as collagen‐1 and collagen‐3, by VSMCs. Abbreviations: ACAT‐1, acyl‐coenzyme A:cholesterol acyltransferase‐1; ABCA1, ATP‐binding cassette transporter A1; DM, diabetes mellitus; HT, hypertension, ICAM‐1, intercellular adhesion molecule‐1; M‐CSF, macrophage colony‐stimulating factor; NO, nitric oxide; VCAM‐1, vascular adhesion molecule‐1.


Figure 7. Expression of human omentin‐1 in epicardial adipose tissue. These pictures (Alexa Fluor 488 confocal images) show fluorescent immunohistochemistry staining of human omentin‐1 (green) in epicardial adipose tissues in CAD and non‐CAD patients.


Figure 8. Intracellular signaling pathways for multiple beneficial effects of omentin‐1. This figure illustrates the secretion source, intracellular signals, and main beneficial effects of omentin‐1. Abbreviations: AMPK, AMP‐activated protein kinase; eNOS, endothelial nitric oxide synthase; ERK, extracellular signal‐regulated kinase; JNK, c‐Jun N‐terminal kinase; MAPK, mitogen‐activated protein kinase; NF‐κB, nuclear factor‐κB; PI3K, phosphoinositide 3‐kinase.
References
 1.Al‐Gareeb AI, Alrubai HF, Suliaman SM. Effects of gliclazide add on metformin on serum omentin‐1 levels in patients with type 2 diabetes mellitus. Indian J Endocrinol Metab 20: 195‐198, 2016.
 2.Alcelik A, Tosun M, Ozlu MF, Eroglu M, Aktas G, Kemahi E, Savli H, Yazici M. Serum levels of omentin in end‐stage renal disease patients. Kidney Blood Press Res 35: 511‐516, 2012.
 3.Aleksandrova K, di Giuseppe R, Isermann B, Biemann R, Schulze M, Wittenbecher C, Fritsche A, Lehmann R, Menzel J, Weikert C, Pischon T, Boeing H. Circulating omentin as a novel biomarker for colorectal cancer risk: Data from the EPIC‐Potsdam Cohort Study. Cancer Res 76: 3862‐3871, 2016.
 4.Assadi M, Salimipour H, Akbarzadeh S, Nemati R, Jafari SM, Bargahi A, Samani Z, Seyedabadi M, Sanjdideh Z, Nabipour I. Correlation of circulating omentin‐1 with bone mineral density in multiple sclerosis: The crosstalk between bone and adipose tissue. PLOS ONE 6: e24240, 2011.
 5.Badran M, Ayas N, Laher I. Cardiovascular complications of sleep apnea: Role of oxidative stress. Oxid Med Cell Longev 2014: 985258, 2014.
 6.Balli U, Bozkurt Dogan S, Ongoz Dede F, Sertoglu E, Keles GC. The levels of visceral adipose tissue‐derived serpin, omentin‐1 and tumor necrosis factor‐α in the gingival crevicular fluid of obese patients following periodontal therapy. J Oral Sci 58: 465‐473, 2016.
 7.Barker G, Lim R, Georgiou HM, Lappas M. Omentin‐1 is decreased in maternal plasma, placenta and adipose tissue of women with pre‐existing obesity. PLOS ONE 7: e42943, 2012.
 8.Barraco GM, Luciano R, Semeraro M, Prieto‐Hontoria PL, Manco M. Recently discovered adipokines and cardio‐metabolic comorbidities in childhood obesity. Int J Mol Sci 15: 19760‐19776, 2014.
 9.Bekaert M, Ouwens DM, Hörbelt T, Van de Velde F, Fahlbusch P, Herzfeld de Wiza D, Van Nieuwenhove Y, Calders P, Praet M, Hoorens A, Geerts A, Verhelst X, Kaufman JM, Lapauw B. Reduced expression of chemerin in visceral adipose tissue associates with hepatic steatosis in patients with obesity. Obesity (Silver Spring) 24: 2544‐2552, 2016.
 10.Berti L, Hartwig S, Irmler M, Rädle B, Siegel‐Axel D1, Beckers J, Lehr S, Al‐Hasani H, Häring HU, Hrabě de Angelis M, Staiger H. Impact of fibroblast growth factor 21 on the secretome of human perivascular preadipocytes and adipocytes: A targeted proteomics approach. Arch Physiol Biochem 5: 1‐8, 2016.
 11.Boron D, Czerny B, Bartkowiak‐Wieczorek J, Sieron D, Wolski H. Omentin polymorphism and its relations to bone mineral density in women. Arch Med Res 46: 173‐180, 2015.
 12.Bozkurt Doğan Ş, Öngöz Dede F, Ballı U, Sertoğlu E. Levels of vaspin and omentin‐1 in gingival crevicular fluid as potential markers of inflammation in patients with chronic periodontitis and type 2 diabetes mellitus. J Oral Sci 58:379‐389, 2016.
 13.Britton KA, Fox CS. Ectopic fat depots and cardiovascular disease. Circulation 124: e837‐e841, 2011.
 14.Brunetti L, Di Nisio C, Recinella L, Chiavaroli A, Leone S, Ferrante C, Orlando G, Vacca M. Effects of vaspin, chemerin and omentin‐1 on feeding behavior and hypothalamic peptide gene expression in the rat. Peptides 32: 1866‐1871, 2011.
 15.Brunetti L, Orlando G, Ferrante C, Recinella L, Leone S, Chiavaroli A, Di Nisio C, Shohreh R, Manippa F, Ricciuti A, Vacca M. Orexigenic effects of omentin‐1 related to decreased CART and CRH gene expression and increased norepinephrine synthesis and release in the hypothalamus. Peptides 44: 66‐74, 2013.
 16.Brunetti L, Leone S, Orlando G, Ferrante C, Recinella L, Chiavaroli A, Di Nisio C, Shohreh R, Manippa F, Ricciuti A, Vacca M. Hypotensive effects of omentin‐1 related to increased adiponectin and decreased interleukin‐6 in intra‐thoracic pericardial adipose tissue. Pharmacol Rep 66: 991‐995, 2014.
 17.Cantarini L, Simonini G, Fioravanti A, Generoso M, Bacarelli MR, Dini E, Galeazzi M, Cimaz R. Circulating levels of the adipokines vaspin and omentin in patients with juvenile idiopathic arthritis, and relation to disease activity. Clin Exp Rheumatol 29: 1044‐1048, 2011.
 18.Cao H. Adipocytokines in obesity and metabolic disease. J Endocrinol 220: T47‐T59, 2014.
 19.Catli G, Anik A, Abaci A, Kume T, Bober E. Low omentin‐1 levels are related with clinical and metabolic parameters in obese children. Exp Clin Endocrinol Diabetes 121: 595‐600, 2013.
 20.Cătoi AF, Suciu Ş, Pârvu AE, Copăescu C, Galea RF, Buzoianu AD, Vereşiu IA, Cătoi C, Pop ID. Increased chemerin and decreased omentin‐1 levels in morbidly obese patients are correlated with insulin resistance, oxidative stress and chronic inflammation. Clujul Med 87: 19‐26, 2014.
 21.Cerit ET, Akturk M, Altinova AE, Tavil Y, Ozkan C, Yayla C, Altay M, Demirtas C, Cakir N. Evaluation of body composition changes, epicardial adipose tissue, and serum omentin‐1 levels in overt hypothyroidism. Endocrine 49: 196‐203, 2015.
 22.Chen Q, Shang X, Yuan M, Liang L, Zhong X. Effect of atorvastatin on serum omentin‐1 in patients with coronary artery disease. Coron Artery Dis 28: 44‐51, 2017.
 23.Cheng X. Elucidating the pathophysiological significance of circulating omentin levels: is higher better? Atherosclerosis 251:522‐524, 2016.
 24.Choi JH, Rhee EJ, Kim KH, Woo HY, Lee WY, Sung KC. Plasma omentin‐1 levels are reduced in non‐obese women with normal glucose tolerance and polycystic ovary syndrome. Eur J Endocrinol 165: 789‐96, 2011.
 25.Cloix L, Reverchon M, Cornuau M, Froment P, Ramé C, Costa C, Froment G, Lecomte P, Chen W, Royère D, Guerif F, Dupont J. Expression and regulation of INTELECTIN1 in human granulosa‐lutein cells: Role in IGF‐1‐induced steroidogenesis through NAMPT. Biol Reprod 91: 50, 2014.
 26.Dayem SM, Battah AA, Shehaby AE. Cardiac affection in type 1 diabetic patients in relation to omentin. Open Access Maced J Med Sci 3: 699‐704, 2015.
 27.de Souza Batista CM, Yang RZ, Lee MJ, Glynn NM, Yu DZ, Pray J, Ndubuizu K, Patil S, Schwartz A, Kligman M, Fried SK, Gong DW, Shuldiner AR, Pollin TI, McLenithan JC. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 56: 1655‐1661, 2007.
 28.Du Y, Ji Q, Cai L, Huang F, Lai Y, Liu Y, Yu J, Han B, Zhu E, Zhang J, Zhou Y, Wang Z, Zhao Y. Association between omentin‐1 expression in human epicardial adipose tissue and coronary atherosclerosis. Cardiovasc Diabetol 15: 90, 2016.
 29.Duan XY, Xie PL, Ma YL, Tang SY. Omentin inhibits osteoblastic differentiation of calcifying vascular smooth muscle cells through the PI3K/Akt pathway. Amino Acids 41: 1223‐1231, 2011.
 30.Eisinger K, Krautbauer S, Wiest R, Karrasch T, Hader Y, Scherer MN, Farkas S, Aslanidis C, Buechler C. Portal vein omentin is increased in patients with liver cirrhosis but is not associated with complications of portal hypertension. Eur J Clin Invest 43: 926‐932, 2013.
 31.Fain JN, Sacks HS, Buehrer B, Bahouth SW, Garrett E, Wolf RY, Carter RA, Tichansky DS, Madan AK. Identification of omentin mRNA in human epicardial adipose tissue: Comparison to omentin in subcutaneous, internal mammary artery periadventitial and visceral abdominal depots. Int J Obes (Lond) 32: 810‐815, 2008.
 32.Feng WH, Yuan XW, Tong GY, Wang WM, Hu Y, Shen SM, Li P, Bi Y, Hu J, Shao LL, Dai YY, Liu YQ, Xiang SK, Yang DH, Zhu DL. Correlated increase of omentin‐1 and adiponectin by exenatide, avandamet and dietary change in diet‐induced obese rats. Folia Biol (Praha) 59: 217‐224, 2013.
 33.Fioravanti A, Simonini G, Cantarini L, Generoso M, Galeazzi M, Bacarelli MR, Cimaz R. Circulating levels of the adipocytokines vaspin and omentin in patients with Kawasaki disease. Rheumatol Int 32: 1481‐1482, 2012.
 34.Gaborit B, Venteclef N, Ancel P, Pelloux V, Gariboldi V, Leprince P, Amour J, Hatem SN, Jouve E, Dutour A, Clément K. Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri‐atrial, peri‐ventricular, or peri‐coronary location. Cardiovasc Res 108: 62‐73, 2015.
 35.Gołąbek K, Ostrowska Z, Ziora K, Oświęcimska J, Świętochowska E, Marek B, Kajdaniuk D, Strzelczyk J, Kos‐Kudła B. Association between omentin‐1, bone metabolism markers, and cytokines of the RANKL/RANK/OPG system in girls with anorexia nervosa. Endokrynol Pol 66: 514‐520, 2015.
 36.Gómez‐Hernández A, Beneit N, Díaz‐Castroverde S, Escribano Ó. Differential role of adipose tissues in obesity and related metabolic and vascular complications. Int J Endocrinol 2016: 1216783, 2016.
 37.Greulich S, Chen WJ, Maxhera B, Rijzewijk LJ, van der Meer RW, Jonker JT, Mueller H, de Wiza DH, Floerke RR, Smiris K, Lamb HJ, de Roos A, Bax JJ, Romijn JA, Smit JW, Akhyari P, Lichtenberg A, Eckel J, Diamant M, Ouwens DM. Cardioprotective properties of omentin‐1 in type 2 diabetes: Evidence from clinical and in vitro studies. PLOS ONE 8: e59697, 2013.
 38.Gu N, Kang G, Jin C, Xu Y, Zhang Z, Erle DJ, Zhen G. Intelectin is required for IL‐13‐induced monocyte chemotactic protein‐1 and ‐3 expression in lung epithelial cells and promotes allergic airway inflammation. Am J Physiol Lung Cell Mol Physiol 298: L290‐L296, 2010.
 39.Gu N, Dong Y, Tian Y, Di Z, Liu Z, Chang M, Jia X, Qian Y, Zhang W. Anti‐apoptotic and angiogenic effects of intelectin‐1 in rat cerebral ischemia. Brain Res Bull 130: 27‐35, 2016.
 40.Güneş M, Bukan N. Examination of angiopoietin‐like protein 4, neuropeptide Y, omentin‐1 levels of obese and non‐obese patients with polycystic ovary syndrome. Gynecol Endocrinol 31: 903‐906, 2015.
 41.Guo LJ, Jiang TJ, Liao L, Liu H, He HB. Relationship between serum omentin‐1 level and bone mineral density in girls with anorexia nervosa. J Endocrinol Invest 36: 190‐194, 2013.
 42.Guzik TJ, Mangalat D, Korbut R. Adipocytokines—novel link between inflammation and vascular function? J Physiol Pharmacol 57: 505‐528, 2006.
 43.Halabis M, Dziedzic M, Warchulinska J, Kaznowska‐Bystryk I, Solski J. Omentin—a new adipokine with many roles to play. Curr Issues Pharm Med Sci 28: 176‐180, 2015.
 44.Hansson GK, Libby P. The immune response in atherosclerosis: A double‐edged sword. Nat Rev Immunol 6: 508‐519, 2006.
 45.Harada K, Shibata R, Ouchi N, Tokuda Y, Funakubo H, Suzuki M, Kataoka T, Nagao T, Okumura S, Shinoda N, Kato B, Sakai S, Kato M, Marui N, Ishii H, Amano T, Matsubara T, Murohara T. Increased expression of the adipocytokine omentin in the epicardial adipose tissue of coronary artery disease patients. Atherosclerosis 251: 299‐304, 2016.
 46.Harmon JB, Sanders AE, Wilder RS, Essick GK, Slade GD, Hartung JE, Nackley AG. Circulating omentin‐1 and chronic painful temporomandibular disorders. J Oral Facial Pain Headache 30: 203‐209, 2016.
 47.Herder C, Ouwens DM, Carstensen M, Kowall B, Huth C, Meisinger C, Rathmann W, Roden M, Thorand B. Adiponectin may mediate the association between omentin, circulating lipids and insulin sensitivity: Results from the KORA F4 study. Eur J Endocrinol 172: 423‐432, 2015.
 48.Hiramatsu‐Ito M, Shibata R, Ohashi K, Uemura Y, Kanemura N, Kambara T, Enomoto T, Yuasa D, Matsuo K, Ito M, Hayakawa S, Ogawa H, Otaka N, Kihara S, Murohara T, Ouchi N. Omentin attenuates atherosclerotic lesion formation in apolipoprotein E‐deficient mice. Cardiovasc Res 110: 107‐117, 2016.
 49.Huang Y, Lin Y, Zhang S, Wang Z, Zhang J, Chang C, Liu L, Ji Q, Liu X. Circulating omentin‐1 levels are decreased in dilated cardiomyopathy patients with overt heart failure. Dis Markers 2016: 6762825, 2016.
 50.Iacobellis G, Bianco AC. Epicardial adipose tissue: Emerging physiological, pathophysiological and clinical features. Trends Endocrinol Metab 22: 450‐457, 2011.
 51.Jaikanth C, Gurumurthy P, Cherian KM, Indhumathi T. Emergence of omentin as a pleiotropic adipocytokine. Exp Clin Endocrinol Diabetes 121: 377‐383, 2013.
 52.Jialal I, Devaraj S, Kaur H, Adams‐Huet B, Bremer AA. Increased chemerin and decreased omentin‐1 in both adipose tissue and plasma in nascent metabolic syndrome. J Clin Endocrinol Metab 98: E514‐E517, 2013.
 53.Jung CH, Jung SH, Kim BY, Kim CH, Kang SK, Mok JO. Association of serum omentin levels with cardiac autonomic neuropathy in patients with type 2 diabetes mellitus: a hospital‐based study. Cardiovasc Diabetol 14: 140, 2015.
 54.Kabiri A, Hosseinzadeh‐Attar MJ, Haghighatdoost F, Eshraghian M, Esmaillzadeh A. Impact of olive oil‐rich diet on serum omentin and adiponectin levels: A randomized cross‐over clinical trial among overweight women. Int J Food Sci Nutr 8: 1‐9, 2016.
 55.Kadoglou NP, Lambadiari V, Gastounioti A, Gkekas C, Giannakopoulas TG, Koulia K, Maratou E, Alepaki M, Kakisis J, Karakitsos P, Nikita KS, Dimitriadis G, Liapis CD. The relationship of novel adipokines, RBP4 and omentin‐1, with carotid atherosclerosis severity and vulnerability. Atherosclerosis 235: 606‐612, 2014.
 56.Kadoglou NP, Tahmatzidis DK, Giannakoulas C, Kapelouzou A, Gkontopoulos A, Parissis J, Lampropoulos S, Kottas G. Serum levels of novel adipokines, omentin‐1 and chemerin, in patients with acute myocardial infarction: KOZANI STUDY. J Cardiovasc Med (Hagerstown) 16: 341‐346, 2015.
 57.Karabulut S, Afsar CU, Karabulut M, Alis H, Bozkurt MA, Aydogan F, Serilmez M, Tas F. Clinical significance of serum omentin‐1 levels in patients with pancreatic adenocarcinoma. BBA Clin 6: 138‐142, 2016.
 58.Kataoka Y, Shibata R, Ohashi K, Kambara T, Enomoto T, Uemura Y, Ogura Y, Yuasa D, Matsuno K, Nagata T, Oba T, Yasukawa H, Numaguchi Y, Sone T, Murohara T, Ouchi N. Omentin prevents myocardial ischemic injury through AMPK‐ and Akt‐dependent mechanisms. J Am Coll Cardiol 63: 2722‐2733, 2014.
 59.Katsi V, Vamvakou G, Lekakis J, Tousoulis D, Stefanadis C, Makris T, Kallikazaros I. Omentin, fat and heart: Classical music with new instruments. Heart Lung Circ 23: 802‐806, 2014.
 60.Kazama K, Usui T, Okada M, Hara Y, Yamawaki H. Omentin plays an anti‐inflammatory role through inhibition of TNF‐α‐induced superoxide production in vascular smooth muscle cells. Eur J Pharmacol 686: 116‐123, 2012.
 61.Kazama K, Okada M, Hara Y, Yamawaki H. A novel adipocytokine, omentin, inhibits agonists‐induced increases of blood pressure in rats. J Vet Med Sci 75: 1029‐1034, 2013.
 62.Kazama K, Okada M, Yamawaki H. A novel adipocytokine, omentin, inhibits monocrotaline‐induced pulmonary arterial hypertension in rats. Biochem Biophys Res Commun 452: 142‐146, 2014.
 63.Kazama K, Okada M, Yamawaki H. A novel adiponectine, omentin, inhibits platelet‐derived growth factor‐BB‐induced vascular smooth muscle cell migration through anti‐oxidative mechanism. Am J Physiol Heart Circ Physiol 306: H1714‐H1719, 2014.
 64.Kazama K, Okada M, Yamawaki H. Adipocytokine, omentin inhibits doxorubicin‐induced H9c2 cardiomyoblasts apoptosis through the inhibition of mitochondrial reactive oxygen species. Biochem Biophys Res Commun 457: 602‐607, 2015.
 65.Kerr SC, Carrington SD, Oscarson S, Gallagher ME, Solon M, Yuan S, Ahn JN, Dougherty RH, Finkbeiner WE, Peters MC, Fahy JV. Intelectin‐1 is a prominent protein constituent of pathologic mucus associated with eosinophilic airway inflammation in asthma. Am J Respir Crit Care Med 189: 1005‐1007, 2014.
 66.Kocijancic M, Vujicic B, Racki S, Cubranic Z, Zaputovic L, Dvornil S. Serum omentin‐1 levels as a possible risk factor of mortality in patients with diabetes on haemodialysis. Diabetes Res Clin Pract 110: 44‐50, 2015.
 67.Kocijancic M, Cubranic Z, Vujicic B, Racki S, Dvornik S, Zaputovic L. Soluble intracellular adhesion molecule‐1 and omentin‐1 as potential biomarkers of subclinical atherosclerosis in hemodialysis patients. Int Urol Nephrol 48: 1145‐1154, 2016.
 68.Kohan L, Safarpur M, Abdollahi H. Omentin‐1 rs2274907 and resistin rs1862513 polymorphisms influence genetic susceptibility to nonalcoholic fatty liver disease. Mol Biol Res Commun 5: 11‐17, 2016.
 69.Komiya T, Tanigawa Y, Hirohashi S. Cloning of the novel gene intelectin, which is expressed in intestinal paneth cells in mice. Biochem Biophys Res Commun 251: 759‐762, 1998.
 70.Kukla M, Waluga M, Adamek B, Zalewska‐Ziob M, Kasperczyk J, Gabriel A, Bułdak RJ, Sobala‐Szczygieł B, Kępa L, Ziora K, Żwirska‐Korczala K, Surma E, Sawczyn T, Hartleb M. Omentin serum concentration and hepatic expression in chronic hepatitis C patients—together or apart? Pol J Pathol 66: 231‐238, 2015.
 71.Kuperman DA, Lewis CC, Woodruff PG, Rodriguez MW, Yang YH, Dolganov GM, Fahy JV, Erle DJ. Dissecting asthma using focused transgenic modeling and functional genomics. J Allergy Clin Immunol 116: 305‐311, 2005.
 72.Lee JK, Schnee J, Pang M, Wolfert M, Baum LG, Moremen KW, Pierce M. Human homologs of the Xenopus oocyte cortical granule lectin XL35. Glycobiology 11: 65‐73, 2011.
 73.Li D, Mei H, Pu J, Xiang X, Zhao X, Qu H, Huang K, Zheng L, Tong Q. Intelectin 1 suppresses the growth, invasion and metastasis of neuroblastoma cells through up‐regulation of N‐myc downstream regulated gene 2. Mol Cancer 14: 47, 2015.
 74.Li D, Zhao X, Xiao Y, Mei H, Pu J, Xiang X, Jiao W, Song H, Qu H, Huang K, Zheng L, Tong Q. Intelectin 1 suppresses tumor progression and is associated with improved survival in gastric cancer. Oncotarget 6: 16168‐16182, 2015.
 75.Li XP, Zeng S, Wang M, Wu XP, Liao EY. Relationships between serum omentin‐1, body fat mass and bone mineral density in healthy Chinese male adults in Changsha area. J Endocrinol Invest 37: 991‐1000, 2014.
 76.Libby P. Inflammation and atherosclerosis. Arterioscler Thromb Vasc Biol 32: 2045‐2051, 2012.
 77.Liu H, Wu J, Wang H, Sheng L, Tang N, Li Y, Hao T. Association of serum omentin‐1 concentrations with the presence and severity of preeclampsia. Ann Clin Biochem 52: 245‐250, 2015.
 78.Liu R, Wang X, Bu P. Omentin‐1 is associated with carotid atherosclerosis in patients with metabolic syndrome. Diabetes Res Clin Pract 93: 21‐25, 2011.
 79.Luedde M, Benz F, Niedeggen J, Vucur M, Hippe HJ, Spehlmann ME, Schueller F, Loosen S, Frey N, Trautwein C, Koch A, Luedde T, Tacke F, Roderburg C. Elevated omentin serum levels predict long‐term survival in critically ill patients. Dis Markers 2016: 3149243, 2016.
 80.Luque‐Ramírez M, Martínez‐García MÁ, Montes‐Nieto R, Fernández‐Durán E, Insenser M, Alpañés M, Escobar‐Morreale HF. Sexual dimorphism in adipose tissue function as evidenced by circulating adipokine concentrations in the fasting state and after an oral glucose challenge. Hum Reprod 28: 1908‐1918, 2013.
 81.Maruyama S, Shibata R, Kikuchi R, Izumiya Y, Rokutanda T, Araki S, Kataoka Y, Ohashi K, Daida H, Kihara S, Ogawa H, Murohara T, Ouchi N. Fat‐derived factor omentin stimulates endothelial cell function and ischemia‐induced revascularization via endothelial nitric oxide synthase‐dependent mechanism. J Biol Chem 287: 408‐417, 2012.
 82.Matsuo K, Shibata R, Ohashi K, Kambara T, Uemura Y, Hiramatsu‐Ito M, Enomoto T, Yuasa D, Joki Y, Ito M, Hayakawa S, Ogawa H, Kihara S, Murohara T, Ouchi N. Omentin functions to attenuate cardiac hypertrophic response. J Mol Cell Cardiol 79: 195‐202, 2015.
 83.Menzel J, di Giuseppe R, Biemann R, Wittenbecher C, Aleksandrova K, Pischon T, Fritsche A, Schulze MB, Boeing H, Isermann B, Weikert C. Omentin‐1 and risk of myocardial infarction and stroke: Results from the EPIC‐Potsdam cohort study. Atherosclerosis 251: 415‐421, 2016.
 84.Menzel J, di Giuseppe R, Biemann R, Aleksandrova K, Kuxhaus O, Wittenbecher C, Fritsche A, Schulze MB, Isermann B, Boeing H. Association between omentin‐1, adiponectin and bone health under consideration of osteoprotegerin as possible mediator. J Endocrinol Invest 39: 1347‐1355, 2016.
 85.Miura S, Asano Y, Saigusa R, Yamashita T, Taniguchi T, Takahashi T, Ichimura Y, Toyama T, Tamaki Z, Tada Y, Sugaya M, Sato S, Kadono T. Serum omentin levels: A possible contribution to vascular involvement in patients with systemic sclerosis. J Dermatol 42: 461‐466, 2015.
 86.Moreno‐Navarrete JM, Catalán V, Ortega F, Gómez‐Ambrosi J, Ricart W, Frühbeck G, Fernández‐Real JM. Circulating omentin concentration increases after weight loss. Nutr Metab (Lond) 7: 27, 2010.
 87.Moreno‐Navarrete JM, Ortega F, Castro A, Sabater M, Ricart W, Fernández‐Real JM. Circulating omentin as a novel biomarker of endothelial dysfunction. Obesity (Silver Spring) 19: 1552‐1559, 2011.
 88.Nagata S, Nakanishi M, Nanba R, Fujita N. Developmental expression of XEEL, a novel molecule of the Xenopus oocyte cortical granule lectin family. Dev Genes Evol 213: 368‐370, 2003.
 89.Narumi T, Watanabe T, Kadowaki S, Kinoshita D, Yokoyama M, Honda Y, Otaki Y, Nishiyama S, Takahashi H, Arimoto T, Shishido T, Miyamoto T, Kubota I. Impact of serum omentin‐1 levels on cardiac prognosis in patients with heart failure. Cardiovasc Diabetol 13: 84, 2014.
 90.Nassif WM, Amin AI, Hassan ZA, Abdelaziz DH. Changes of serum omentin‐1 levels and relationship between omentin‐1 and insulin resistance in chronic hepatitis C patients. EXCLI J 12: 924‐932, 2013.
 91.Onur I, Oz F, Yildiz S, Oflaz H, Sigirci S, Elitok A, Pilten S, Karaayvaz EB, Cizgici AY, Kaya MG, Onur ST, Sahin I, Dinckal HM. Serum omentin 1 level is associated with coronary artery disease and its severity in postmenopausal women. Angiology 65: 896‐900, 2014.
 92.Onur I, Oz F, Yildiz S, Kuplay H, Yucel C, Sigirci S, Elitok A, Pilten S, Kasali K, Yasar Cizgici A, Erentug V, Dinckal HM. A decreased serum omentin‐1 level may be an independent risk factor for peripheral arterial disease. Int Angiol 33: 455‐460, 2014.
 93.Oświęcimska J, Suwała A, Świętochowska E, Ostrowska Z, Gorczyca P, Ziora‐Jakutowicz K, Machura E, Szczepańska M, Kukla M, Stojewska M, Ziora D, Ziora K. Serum omentin levels in adolescent girls with anorexia nervosa and obesity. Physiol Res 64: 701‐709, 2015.
 94.Pan BL, Ma RM. Correlation of serum omentin‐1 and chemerin with gestational diabetes mellitus. Nan Fang Yi Ke Da Xue Xue Bao 36:1231‐1236, 2016.
 95.Pan HY, Guo L, Li Q. Changes of serum omentin‐1 levels in normal subjects and in patients with impaired glucose regulation and with newly diagnosed and untreated type 2 diabetes. Diabetes Res Clin Pract 88: 29‐33, 2010.
 96.Panagiotou G, Mu L, Na B, Mukamal KJ, Mantzoros CS. Circulating irisin, omentin‐1, and lipoprotein subparticles in adults at higher cardiovascular risk. Metabolism 63: 1265‐1271, 2014.
 97.Pickering RT, Lee MJ, Karastergiou K, Gower A, Fried SK. Depot dependent effects of dexamethasone on gene expression in human omental and abdominal subcutaneous adipose tissues from obese women. PLOS ONE 11: e0167337, 2016.
 98.Polkowska A, Szczepaniak I, Bossowski A. Assessment of serum concentrations of ghrelin, obestatin, omentin‐1, and apelin in children with type 1 diabetes. Biomed Res Int 2016: 8379294, 2016.
 99.Pourbehi MR, Zahedi T, Darabi H, Ostovar A, Assadi M, Nabipour I. Omentin‐1 and nonfatal ischemic heart diseases in postmenopausal women: A population‐based study. Endocr Pract 22: 780‐785, 2016.
 100.Prats‐Puig A, Bassols J, Bargalló E, Mas‐Parareda M, Ribot R, Soriano‐Rodríguez P, Berengüí À, Díaz M, de Zegher F, Ibánez L, López‐Bermejo A. Toward an early marker of metabolic dysfunction: Omentin‐1 in prepubertal children. Obesity (Silver Spring) 19: 1905‐1907, 2011.
 101.Qi D, Tang X, He J, Wang D, Zhao Y, Deng W, Deng X, Zhou G, Xia J, Zhong X, Pu S. Omentin protects against LPS‐induced ARDS through suppressing pulmonary inflammation and promoting endothelial barrier via an Akt/eNOS‐dependent mechanism. Cell Death Dis 7: e2360, 2016.
 102.Reyman M, Verrijn Stuart AA, van Summeren M, Rakhshandehroo M, Nuboer R, de Boer FK, van den Ham HJ, Kalkhoven E, Prakken B, Schipper HS. Vitamin D deficiency in childhood obesity is associated with high levels of circulating inflammatory mediators, and low insulin sensitivity. Int J Obes (Lond) 38: 46‐52, 2014.
 103.Robinson C, Tsang L, Solomon A, Woodiwiss AJ, Gunter S, Millen AM, Norton GR, Fernandez‐Lopez MJ, Hollan I, Dessein PH. Omentin concentrations are independently associated with those of matrix metalloproteinase‐3 in patients with mild but not severe rheumatoid arthritis. Rheumatol Int 37: 3‐11, 2017.
 104.Saely CH, Leiherer A, Muendlein A, Vonbank A, Rein P, Geiger K, Malin C, Drexel H. Coronary patients with high plasma omentin are at a higher cardiovascular risk. Data Brief 6: 158‐161, 2015.
 105.Saely CH, Leiherer A, Muendlein A, Vonbank A, Rein P, Geiger K, Malin C, Drexel H. High plasma omentin predicts cardiovascular events independently from the presence and extent of angiographically determined atherosclerosis. Atherosclerosis 244: 38‐43, 2016.
 106.Sawicka M, Janowska J, Chudek J. Potential beneficial effect of some adipokines positively correlated with the adipose tissue content on the cardiovascular system. Int J Cardiol 222: 581‐589, 2016.
 107.Schäffler A, Neumeier M, Herfarth H, Fürst A, Schölmerich J, Büchler C. Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta 1732: 96‐102, 2005.
 108.Schipper HS, Nuboer R, Prop S, van den Ham HJ, de Boer FK, Kesmir C, Mombers IM, van Bekkum KA, Woudstra J, Kieft JH, Hoefer IE, de Jager W, Prakken B, van Summeren M, Kalkhoven E. Systemic inflammation in childhood obesity: Circulating inflammatory mediators and activated CD14++ monocytes. Diabetologia 55: 2800‐2810, 2012.
 109.Sengul E, Duygulu G, Dindar S, Bunul F. Serum omentin‐1, inflammation and carotid atherosclerosis in patients with non‐diabetic chronic kidney disease. Ren Fail 35: 1089‐1093, 2013.
 110.Senolt L, Polanská M, Filková M, Cerezo LA, Pavelka K, Gay S, Haluzík M, Vencovsky J. Vaspin and omentin: New adipokines differentially regulated at the site of inflammation in rheumatoid arthritis. Ann Rheum Dis 69: 1410‐1411, 2010.
 111.Shen XD, Zhang L, Che H, Zhang YY, Yang C, Zhou J, Liang CZ. Circulating levels of adipocytokine omentin‐1 in patients with renal cell cancer. Cytokine 77: 50‐55, 2016.
 112.Shibata R, Ouchi N, Kikuchi R, Takahashi R, Takeshita K, Kataoka Y, Ohashi K, Ikeda N, Kihara S, Murohara T. Circulating omentin is associated with coronary artery disease in men. Atherosclerosis 219: 811‐814, 2011.
 113.Shibata R, Ouchi N, Takahashi R, Terakura Y, Ohashi K, Ikeda N, Higuchi A, Terasaki H, Kihara S, Murohara T. Omentin as a novel biomarker of metabolic risk factors. Diabetol Metab Syndr 4: 37, 2012.
 114.Shin K, Wakabayashi H, Yamauchi K, Yaeshima T, Iwatsuki K. Recombinant human intelectin binds bovine lactoferrin and its peptides. Biol Pharm Bull 31: 1605‐1608, 2008.
 115.Shoji H, Ikenaka K, Nakakita S, Hayama K, Hirabayashi J, Arata Y, Kasai K, Nishi N, Nakamura T. Xenopus galectin‐VIIa binds N‐glycans of members of the cortical granule lectin family (xCGL and xCGL2). Glycobiology 15: 709‐720, 2005.
 116.Sit M, Aktas G, Yilmaz EE, Alcelik A, Terzi EH, Tosun M. Effects of the inflammatory response on serum omentin levels in early acute and chronic pancreatitis. Clin Ter 165: e148‐e152, 2014.
 117.Sperling M, Grzelak T, Pelczyńska M, Jasinska P, Bogdanski P, Pupek‐Musialik D, Czyzewska K. Concentrations of omentin and vaspin versus insulin resistance in obese individuals. Biomed Pharmacother 83: 542‐547, 2016.
 118.Stejskal D, Vaclavik J, Smekal A, Svobodova G, Richterova R, Svestak M. Omentin‐1 levels in patients with premature coronary artery disease, metabolic syndrome and healthy controls. Short communication. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 160: 219‐221, 2016.
 119.Suzuki YA, Shin K, Lönnerdal B. Molecular cloning and functional expression of a human intestinal lactoferrin receptor. Biochemistry 40: 15771‐15779, 2001.
 120.Svensson H, Odén B, Edén S, Lönn M. Adiponectin, chemerin, cytokines, and dipeptidyl peptidase 4 are released from human adipose tissue in a depot‐dependent manner: An in vitro system including human serum albumin. BMC Endocr Disord 14: 7, 2014.
 121.Szydło B, Kiczmer P, Świętochowska E, Ostrowska Z. Role of omentin and chemerin in metabolic syndrome and tumor diseases. Postepy Hig Med Dosw (Online) 70: 844‐849, 2016.
 122.Tan BK, Adya R, Farhatullah S, Lewandowski KC, O'Hare P, Lehnert H, Randeva HS. Omentin‐1, a novel adipokine, is decreased in overweight insulin‐resistant women with polycystic ovary syndrome: Ex vivo and in vivo regulation of omentin‐1 by insulin and glucose. Diabetes 57: 801‐808, 2008.
 123.Tan BK, Pua S, Syed F, Lewandowski KC, O'Hare JP, Randeva HS. Decreased plasma omentin‐1 levels in Type 1 diabetes mellitus. Diabet Med 25: 1254‐1255, 2008.
 124.Tan BK, Adya R, Farhatullah S, Chen J, Lehnert H, Randeva HS. Metformin treatment may increase omentin‐1 levels in women with polycystic ovary syndrome. Diabetes 59: 3023‐3031, 2010.
 125.Tan YL, Zheng XL, Tang CK. The protective functions of omentin in cardiovascular diseases. Clin Chim Acta 448: 98‐106, 2015.
 126.Tang YL, Yu J, Zeng ZG, Liu Y, Liu JY, Xu JX. Circulating omentin‐1 levels in women with polycystic ovary syndrome: A meta‐analysis. Gynecol Endocrinol 2: 1‐6, 2016.
 127.Tanaka K. Expression of Toll‐like receptors in the intestinal mucosa of patients with inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2: 193‐196, 2008.
 128.Tao S, Huang YQ, Cai AP, Huang C, Zhang Y, Tang ST, Yu XJ, Zhou D, Tan N, Feng YQ. Association of serum omentin‐1 concentrations with the presence of atrial fibrillation. Med Sci Monit 22: 4749‐4754, 2016.
 129.Tekce H, Tekce BK, Aktas G, Alcelik A, Sengul E. Serum omentin‐1 levels in diabetic and nondiabetic patients with chronic kidney disease. Exp Clin Endocrinol Diabetes 122: 451‐456, 2014.
 130.Tohidi M, Akbarzadeh S, Larijani B, Kalantarhormozi M, Ostovar A, Assadi M, Vahdat K, Farrokhnia M, Sanjdideh Z, Amirinejad R, Nabipour I. Omentin‐1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women. Bone 51: 867‐881, 2012.
 131.Tsuji S, Uehori J, Matsumoto M, Suzuki Y, Matsuhisa A, Toyoshima K, Seya T. Human intelectin is a novel soluble lectin that recognizes galactofuranose in carbohydrate chains of bacterial cell wall. J Biol Chem 276: 23456‐23463, 2001.
 132.Tsuji S, Yamashita M, Nashiyama A, Shinohara T, Li Z, Myrvik QN, Hoffman DR, Henriksen RA, Shibata Y. Differential structure and activity between human and mouse intelectin‐1: Human intelectin‐1 is a disulfide‐linked trimer, whereas mouse homologue is a monomer. Glycobiology 17: 1045‐1051, 2007.
 133.Tsuji S, Tsuura Y, Morohoshi T, Shinohara T, Oshita F, Yamada K, Kameda Y, Ohtsu T, Nakamura Y, Miyagi Y. Secretion of intelectin‐1 from malignant pleural mesothelioma into pleural effusion. Br J Cancer 103: 517‐523, 2010.
 134.Ucgun T, Başar C, Memişoğulları R, Demirin H, Türker Y, Aslantaş Y. Serum visfatin and omentin levels in slow coronary flow. Rev Port Cardiol 33: 789‐794, 2014.
 135.Uemura Y, Shibata R, Kanemura N, Ohashi K, Kambara T, Hiramatsu‐Ito M, Enomoto T, Yuasa D, Joki Y, Matsuo K, Ito M, Hayakawa S, Ogawa H, Murohara T, Ouchi N. Adipose‐derived protein omentin prevents neointimal formation after arterial injury. FASEB J 29: 141‐151, 2015.
 136.Uyeturk U, Alcelik A, Aktas G, Tekce BK. Post‐treatment plasma omentin levels in patients with stage III colon carcinoma. J BUON 19: 681‐685, 2014.
 137.Uyeturk U, Sarıcı H, Kın Tekce B, Eroglu M, Kemahlı E, Uyeturk U, Gucuk A. Serum omentin level in patients with prostate cancer. Med Oncol 31: 923, 2014.
 138.Uygur F, Tanrıverdi H, Can M, Erboy F, Altınsoy B, Atalay F, Ornek T, Damar M, Kokturk F, Tor M. Association between continuous positive airway pressure and circulating omentin levels in patients with obstructive sleep apnoea. Sleep Breath 20: 939‐945, 2016.
 139.Wan W, Li Q, Zhang F, Zheng G, Lv Y, Wan G, Jin X. Serum and vitreous concentrations of omentin‐1 in diabetic retinopathy. Dis Markers 2015: 754312, 2015.
 140.Wang Q, Feng X, Zhou C, Li P, Kang J. Decreased levels of serum omentin‐1 in patients with obstructive sleep apnoea syndrome. Ann Clin Biochem 50: 230‐235, 2013.
 141.Wangkanont K, Wesener DA, Vidani JA, Kiessling LL, Forest KT. Structures of Xenopus embryonic epidermal lectin reveal a conserved mechanism of microbial glycan recognition. J Biol Chem 291: 5596‐5610, 2016.
 142.Washimi K, Yokose T, Yamashita M, Kageyama T, Suzuki K, Yoshihara M, Miyagi Y, Hayashi H, Tsuji S. Specific expression of human intelectin‐1 in malignant pleural mesothelioma and gastrointestinal goblet cells. PLOS ONE 7: e39889, 2012.
 143.Watanabe K, Watanabe R, Konii H, Shirai R, Sato K, Matsuyama T, Ishibashi‐Ueda H, Koba S, Kobayashi Y, Hirano T, Watanabe T. Counteractive effects of omentin‐1 against atherogenesis. Cardiovasc Res 110: 118‐128, 2016.
 144.Wesener DA, Wangkanont K, McBride R, Song X, Kraft MB, Hodges HL, Zarling LC, Splain RA, Smith DF, Cummings RD, Paulson JC, Forest KT, Kiessling LL. Recognition of microbial glycans by human intelectin. Nat Struct Mol Biol 22: 603‐610, 2015.
 145.Wilms B, Ernst B, Gerig R, Schultes B. Plasma omentin‐1 levels are related to exercise performance in obese women and increase upon aerobic endurance training. Exp Clin Endocrinol Diabetes 123: 187‐192, 2015.
 146.Wrackmeyer U, Hansen GH, Seya T, Danielsen EM. Intelectin: A novel lipid raft‐associated protein in the enterocyte brush border. Biochemistry 45: 9188‐9197, 2006.
 147.Wu QM, Ni HX, Lu X. Changes of adipocytokine expression after diabetic rats received sitagliptin and the molecular mechanism. Asian Pac J Trop Med 9: 893‐897, 2016.
 148.Wu SS, Liang QH, Liu Y, Cui RR, Yuan LQ, Liao EY. Omentin‐1 stimulates human osteoblast proliferation through PI3K/Akt signal pathway. Int J Endocrinol 2013: 368970, 2013.
 149.Xie H, Xie PL, Wu XP, Chen SM, Zhou HD, Yuan LQ, Sheng ZF, Tang SY, Luo XH, Liao EY. Omentin‐1 attenuates arterial calcification and bone loss in osteoprotegerin‐deficient mice by inhibition of RANKL expression. Cardiovasc Res 92: 296‐306, 2011.
 150.Xie H, Xie PL, Luo XH, Wu XP, Zhou HD, Tang SY, Liao EY. Omentin‐1 exerts bone‐sparing effect in ovariectomized mice. Osteoporos Int 23: 1425‐1436, 2012.
 151.Xu L, Zhu GB, Wang L, Wang DF, Jiang XR. Synovial fluid omentin‐1 levels are inversely correlated with radiographic severity of knee osteoarthritis. J Investig Med 60: 583‐586, 2012.
 152.Xu S, Xue Y. Pediatric obesity: Causes, symptoms, prevention and treatment. Exp Ther Med 11: 15‐20, 2016.
 153.Xue Y, Jiang L, Cheng Q, Chen H, Yu Y, Lin Y, Yang X, Kong N, Zhu X, Xu X, Wan W, Zou H. Adipokines in psoriatic arthritis patients: The correlations with osteoclast precursors and bone erosions. PLOS ONE 7: e46740, 2012.
 154.Yamawaki H, Tsubaki N, Mukohda M, Okada M, Hara Y. Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochem Biophys Res Commun 393: 668‐672, 2010.
 155.Yamawaki H, Kuramoto J, Kameshima S, Usui T, Okada M, Hara Y. Omentin, a novel adipocytokine inhibits TNF‐induced vascular inflammation in human endothelial cells. Biochem Biophys Res Commun 408: 339‐343, 2011.
 156.Yan J, Wang J, Zhao Y, Zhang J, Bai C, Zhang C, Zhang C, Li K, Zhang H, Du X, Feng L. Identification of an amphioxus intelectin homolog that preferably agglutinates gram‐positive over gram‐negative bacteria likely due to different binding capacity to LPS and PGN. Fish Shellfish Immunol 33: 11‐20, 2012.
 157.Yang HY, Ma Y, Lu XH, Liang XH, Suo YJ, Huang ZX, Lu DC, Qin YF, Luo ZJ. The correlation of plasma omentin‐1 with insulin resistance in non‐obese polycystic ovary syndrome. Ann Endocrinol (Paris) 76: 620‐627, 2015.
 158.Yang RZ, Shuldiner AR, Gong DW. Cloning of omentin, a new adipokine from human omental fat tissue. NCBI, nucleotide database, accession number: AY549722.
 159.Yang RZ, Lee MJ, Hu H, Pray J, Wu HB, Hansen BC, Shuldiner AR, Fried SK, McLenithan JC, Gong DW. Identification of omentin as a novel depot‐specific adipokine in human adipose tissue: Possible role in modulating insulin action. Am J Physiol Endocrinol Metab 290: E1253‐E1261, 2006.
 160.Yin J, Hou P, Wu Z, Nie Y. Decreased levels of serum omentin‐1 in patients with inflammatory bowel disease. Med Sci Monit 21: 118‐122, 2015.
 161.Yoo HJ, Hwang SY, Hong HC, Choi HY, Yang SJ, Seo JA, Kim SG, Kim NH, Choi KM, Choi DS, Baik SH. Association of circulating omentin‐1 level with arterial stiffness and carotid plaque in type 2 diabetes. Cardiovasc Diabetol 10: 103, 2011.
 162.Yörük U, Yaykaşli KO, Özhan H, Memişoğullari R, Karabacak A, Bulur S, Aslantaş Y, Başar C, Kaya E. Association of omentin Val109Asp polymorphism with coronary artery disease. Anadolu Kardiyol Derg 14: 511‐514, 2014.
 163.Zabetian‐Targhi F, Mirzaei K, Keshavarz SA, Hossein‐Nezhad A. Modulatory role of omentin‐1 in inflammation: Cytokines and dietary intake. J Am Coll Nutr 22: 1‐9, 2016.
 164.Zehsaz F, Farhangi N, Ghahramani M. The response of circulating omentin‐1 concentration to 16‐week exercise training in male children with obesity. Phys Sportsmed 44: 355‐361, 2016.
 165.Zhang C, Zhu KJ, Liu JL, Xu GX, Liu W, Jiang FX, Zheng HF, Quan C. Omentin‐1 plasma levels and omentin‐1 expression are decreased in psoriatic lesions of psoriasis patients. Arch Dermatol Res 307: 455‐459, 2015.
 166.Zhang Q, Zhu L, Zheng M, Fan C, Li Y, Zhang D, He Y, Yang H. Changes of serum omentin‐1 levels in normal subjects, type 2 diabetes and type 2 diabetes with overweight and obesity in Chinese adults. Ann Endocrinol (Paris) 75: 171‐175, 2014.
 167.Zhang TP, Li HM, Leng RX, Li XP, Li XM, Pan HF, Ye DQ. Plasma levels of adipokines in systemic lupus erythematosus patients. Cytokine 86: 15‐20, 2016.
 168.Zhang YY, Zhou LM. Omentin‐1, a new adipokine, promotes apoptosis through regulating Sirt1‐dependent p53 deacetylation in hepatocellular carcinoma cells. Eur J Pharmacol 698: 137‐144, 2013.
 169.Zhao LR, Du YJ, Chen L, Liu ZG, Jia XY, Pan YH, Liu JF, Liu B. Omentin‐1 promotes the growth of neural stem cells via activation of Akt signaling. Mol Med Rep 11: 1859‐1864, 2015.
 170.Zheng L, Weng M, Qi M, Qi T, Tong L, Hou X, Tong Q. Aberrant expression of intelectin‐1 in gastric cancer: Its relationship with clinicopathological features and prognosis. J Cancer Res Clin Oncol 138: 163‐172, 2012.
 171.Zhong X, Li X, Liu F, Tan H, Shang D. Omentin inhibits TNF‐α‐induced expression of adhesion molecules in endothelial cells via ERK/NF‐κB pathway. Biochem Biophys Res Commun 425: 401‐406, 2012.
 172.Zhou JP, Tong XY, Zhu LP, Luo JM, Luo Y, Bai YP, Li CC, Zhang GG. Plasma omentin‐1 level as a predictor of good coronary collateral circulation. J Atheroscler Thromb 2017, in press.
 173.Zhou Y, Wei Y, Wang L, Wang X, Du X, Sun Z, Dong N, Chen X. Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease. Cardiovasc Diabetol 10: 2, 2011.

 

Teaching Material

T. Watanabe, K. Watanabe-Kominato, Y. Takahashi, M. Kojima, R. Watanabe. Adipose Tissue-Derived Omentin-1 Function and Regulation. Compr Physiol 7 2017, 765-781.

Didactic Synopsis

 

Major Teaching Points:

     

  • Omentin-1, also known as intelectin-1, is a recently identified novel adipocytokine that is mainly expressed in visceral fat.

 

     

  • Omentin-1 is downregulated by glucose/insulin and upregulated by fibroblast growth factor-21 and dexamethasone.

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  • Omentin-1 exerts suppressive effects on insulin resistance, atherosclerosis, and inflammation via AMP-activated protein kinase/Akt/nuclear factor-κB/mitogen-activated protein kinase (ERK, JNK, and p38) intracellular signaling pathways.

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  • Circulating omentin-1 is used as a biomarker of obesity, diabetes, metabolic syndrome, atherosclerosis, ischemic heart disease, inflammatory disease, and cancer.

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  • This review provides insights into the potential use of omentin-1 as a biomarker and therapeutic target for these diseases.

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Didactic Legends

The figures-in a freely downloadable PowerPoint format-can be found on the Images tab along with the formal legends published in the article. The following legends to the same figures are written to be useful for teaching.

 

 

Figure 1. Teaching points: Understanding the favorable (+) and unfavorable (-) effects of novel adipocytokines (adiponectin, omentin-1, vaspin, chemerin, resistin, and leptin) on energy homeostasis, glucose metabolism, cardiovascular protection, anti-inflammation response, and antioxidative stress.

Figure 2. Teaching points: Understanding the genomic structure of human omentin gene (A) and the exon-intron junctions (B). Exons are indicated as square boxes and the open reading frame is indicated as black regions. The sequences and numbers of exon junctions are shown above the square boxes. The consensus sequences for splicing are underlined.

Figure 3. Teaching points: Understanding the alignment of amino acid sequences between human omentin-1 and mouse omentin-1. The homologous amino acids are shown in outline characters on black backgrounds, which are 81.5% identical (255/313 amino acids).

Figure 4. Teaching points: Understanding the alignment of amino acid sequence between human omentin-1 and human omentin-2. The homologous amino acids are shown in outline characters on black backgrounds, which are 83.0% identical (264/318 amino acids).

Figure 5. Teaching points: Understanding the expression of human omentin-1 in human vascular cells: human monocytes, human monocyte-derived macrophages (HMDMs), human umbilical vein endothelial cells (HUVECs), and human aortic smooth muscle cells (HASMCs). α-tubulin served as a loading control. Molecular size is expressed in kilodaltons (kDa).

Figure 6. Teaching points: Understanding the mechanisms underlying the atheroprotective effects of omentin-1 in the arterial wall. Omentin-1 prevents atherosclerosis by suppressing the inflammatory responses in endothelial cells (ECs), the adhesion of monocytes (Mo) to ECs, oxidized low-density lipoprotein (LDL)-induced foam cell formation in Mo-derived macrophages, the migration and proliferation of vascular smooth muscle cells (VSMCs), and the production of extracellular matrix (ECM), such as collagen-1 and collagen-3, by VSMCs.

Figure 7. Teaching points: Understanding the expression of human omentin-1 in epicardial adipose tissue in coronary artery disease (CAD) and non-CAD patients. Pictures show that omentin-1 expression (green color) in epicardial adipose tissue is decreased in a CAD patient compared with a non-CAD patient.

Figure 8. Teaching points: Understanding the intracellular signaling pathways for multiple beneficial effects of omentin-1. This figure illustrates the secretion source, intracellular signals, and main beneficial effects of omentin-1.

 


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Article Title: Adipose Tissue‐Derived Omentin‐1 Function and Regulation
 

How to Cite

Takuya Watanabe, Kaho Watanabe‐Kominato, Yui Takahashi, Miho Kojima, Rena Watanabe. Adipose Tissue‐Derived Omentin‐1 Function and Regulation. Compr Physiol 2017, 7: 765-781. doi: 10.1002/cphy.c160043