Unravelling the adiponectin paradox: novel roles of adiponectin in the regulation of cardiovascular disease

British Journal of Pharmacology

Volumn 174, Issue 22, 2017, Pages 4007-4020

  Woodward, Lavinia ^a   Akoumianakis, Ioannis ^a   Antoniades, Charalambos ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPONECTIN; BIOLOGICAL MARKER;

ADIPOSE TISSUE; APOPTOSIS; ATHEROSCLEROSIS; BLOOD VESSEL WALL; CARDIAC MUSCLE; CARDIOVASCULAR DISEASE; HUMAN; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; PROTEIN SYNTHESIS; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; CHEMISTRY; METABOLISM;

ADIPONECTIN; ADIPOSE TISSUE; ANIMALS; BIOMARKERS; CARDIOVASCULAR DISEASES; HUMANS;

EID: 84991628231     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.13619     Document Type: Review

References (158)

1. Alexander SPH, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E et al. (2015a). The concise guide to pharmacology 2015/16: Overview. Br J Pharmacol 172: 5729–5743.
2. Alexander SPH, Cidlowski JA, Kelly E, Marrion N, Peters JA, Benson HE et al. (2015b). The Concise Guide to PHARMACOLOGY 2015/16: Nuclear hormone receptors. Br J Pharmacol 172: 5956–5978.
3. Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE et al. (2015c). The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol 172: 6024–6109.
4. Alexopoulos N, Katritsis D, Raggi P (2014). Visceral adipose tissue as a source of inflammation and promoter of atherosclerosis. Atherosclerosis 233: 104–112.
5. Antoniades C, Shirodaria C, Crabtree M, Rinze R, Alp N, Cunnington C et al. (2007). Altered plasma versus vascular biopterins in human atherosclerosis reveal relationships between endothelial nitric oxide synthase coupling, endothelial function, and inflammation. Circulation 116: 2851–2859.
6. Antoniades C, Antonopoulos AS, Bendall JK, Channon KM (2009). Targeting redox signaling in the vascular wall: from basic science to clinical practice. Curr Pharm Des 15: 329–342.
7. Antonopoulos AS, Tousoulis D, Antoniades C, Miliou A, Hatzis G, Papageorgiou N et al. (2013). Genetic variability on adiponectin gene affects myocardial infarction risk: the role of endothelial dysfunction. Int J Cardiol 168: 326–330.
8. Antonopoulos AS, Margaritis M, Coutinho P, Digby J, Patel R, Psarros C et al. (2014). Reciprocal effects of systemic inflammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol 34: 2151–2159.
9. Antonopoulos AS, Margaritis M, Coutinho P, Shirodaria C, Psarros C, Herdman L et al. (2015). Adiponectin as a link between type 2 diabetes and vascular NADPH oxidase activity in the human arterial wall: the regulatory role of perivascular adipose tissue. Diabetes 64: 2207–2219.
10. Antonopoulos AS, Margaritis M, Verheule S, Recalde A, Sanna F, Herdman L et al. (2016). Mutual regulation of epicardial adipose tissue and myocardial redox state by PPAR-gamma/adiponectin signalling. Circ Res 118: 842–855.
11. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J et al. (1999). Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257: 79–83.
12. Arnaboldi L, Corsini A (2015). Could changes in adiponectin drive the effect of statins on the risk of new-onset diabetes? The case of pitavastatin. Atheroscler Suppl 16: 1–27.
13. Battes LC, Cheng JM, Oemrawsingh RM, Boersma E, Garcia-Garcia HM, de Boer SP et al. (2014). Circulating cytokines in relation to the extent and composition of coronary atherosclerosis: results from the ATHEROREMO-IVUS study. Atherosclerosis 236: 18–24.
14. Behre CJ (2007). Adiponectin: saving the starved and the overfed. Med Hypotheses 69: 1290–1292.
15. Berg AH, Scherer PE (2005). Adipose tissue, inflammation, and cardiovascular disease. Circ Res 96: 939–949.
16. Bermudez EA, Rifai N, Buring J, Manson JE, Ridker PM (2002). Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women. Arterioscler Thromb Vasc Biol 22: 1668–1673.
17. Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A (2005). Resistin, an adipokine with potent proinflammatory properties. J Immunol 174: 5789–5795.
18. Cao Y, Tao L, Yuan Y, Jiao X, Lau WB, Wang Y et al. (2009). Endothelial dysfunction in adiponectin deficiency and its mechanisms involved. J Mol Cell Cardiol 46: 413–419.
19. Chen C, Jiang J, Lu JM, Chai H, Wang X, Lin PH et al. (2010). Resistin decreases expression of endothelial nitric oxide synthase through oxidative stress in human coronary artery endothelial cells. Am J Physiol Heart Circ Physiol 299: H193–H201.
20. Chiba T, Shinozaki S, Nakazawa T, Kawakami A, Ai M, Kaneko E et al. (2008). Leptin deficiency suppresses progression of atherosclerosis in apoE-deficient mice. Atherosclerosis 196: 68–75.
21. Chun HJ, Ali ZA, Kojima Y, Kundu RK, Sheikh AY, Agrawal R et al. (2008). Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis. J Clin Invest 118: 3343–3354.
22. Chung CM, Lin TH, Chen JW, Leu HB, Yang HC, Ho HY et al. (2011). A genome-wide association study reveals a quantitative trait locus of adiponectin on CDH13 that predicts cardiometabolic outcomes. Diabetes 60: 2417–2423.
23. Clasen R, Schupp M, Foryst-Ludwig A, Sprang C, Clemenz M, Krikov M et al. (2005). PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin. Hypertension 46: 137–143.
24. Coelho M, Oliveira T, Fernandes R (2013). Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci 9: 191–200.
25. Coletta DK, Sriwijitkamol A, Wajcberg E, Tantiwong P, Li M, Prentki M et al. (2009). Pioglitazone stimulates AMP-activated protein kinase signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation in human skeletal muscle in vivo: a randomised trial. Diabetologia 52: 723–732.
26. Dastani Z, Hivert MF, Timpson N, Perry JR, Yuan X, Scott RA et al. (2012). Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet 8: e1002607.
27. Denzel MS, Scimia MC, Zumstein PM, Walsh K, Ruiz-Lozano P, Ranscht B (2010). T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Invest 120: 4342–4352.
28. Djaberi R, Schuijf JD, van Werkhoven JM, Nucifora G, Jukema JW, Bax JJ (2008). Relation of epicardial adipose tissue to coronary atherosclerosis. Am J Cardiol 102: 1602–1607.
29. Dong F, Ren J (2009). Adiponectin improves cardiomyocyte contractile function in db/db diabetic obese mice. Obesity (Silver Spring) 17: 262–268.
30. Ebrahimi-Mamaeghani M, Mohammadi S, Arefhosseini SR, Fallah P, Bazi Z (2015). Adiponectin as a potential biomarker of vascular disease. Vasc Health Risk Manag 11: 55–70.
31. Essick EE, Ouchi N, Wilson RM, Ohashi K, Ghobrial J, Shibata R et al. (2011). Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte remodeling. Am J Physiol Heart Circ Physiol 301: H984–H993.
32. Fontana A, Spadaro S, Copetti M, Spoto B, Salvemini L, Pizzini P et al. (2015). Association between resistin levels and all-cause and cardiovascular mortality: a new study and a systematic review and meta-analysis. PLoS One 10: e0120419.
33. Fryer LG, Parbu-Patel A, Carling D (2002). The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 277: 25226–25232.
34. Furuhashi M, Ura N, Higashiura K, Murakami H, Tanaka M, Moniwa N et al. (2003). Blockade of the renin-angiotensin system increases adiponectin concentrations in patients with essential hypertension. Hypertension 42: 76–81.
35. Gasbarrino K, Gorgui J, Nauche B, Cote R, Daskalopoulou SS (2016). Circulating adiponectin and carotid intima-media thickness: A systematic review and meta-analysis. Metabolism 65: 968–986.
36. Gradman AH (2015). LCZ696: the next step in improving RAS inhibition? Curr Hypertens Rep 17: 37.
37. Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R et al. (2002). Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105: 1656–1662.
38. Haass NK, Nassif N, McGowan EM (2015). Switching the sphingolipid rheostat in the treatment of diabetes and cancer comorbidity from a problem to an advantage. Biomed Res Int 2015: 165105.
39. Haddad JJ, Fahlman CS (2002). Redox- and oxidant-mediated regulation of interleukin-10: an anti-inflammatory, antioxidant cytokine? Biochem Biophys Res Commun 297: 163–176.
40. Halberg N, Schraw TD, Wang ZV, Kim JY, Yi J, Hamilton MP et al. (2009). Systemic fate of the adipocyte-derived factor adiponectin. Diabetes 58: 1961–1970.
41. Han X, Boisvert WA (2015). Interleukin-10 protects against atherosclerosis by modulating multiple atherogenic macrophage function. Thromb Haemost 113: 505–512.
42. Hao G, Li W, Guo R, Yang JG, Wang Y, Tian Y et al. (2013). Serum total adiponectin level and the risk of cardiovascular disease in general population: a meta-analysis of 17 prospective studies. Atherosclerosis 228: 29–35.
43. Hashimoto T, Kihara M, Imai N, Yoshida S, Shimoyamada H, Yasuzaki H et al. (2007). Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis. Am J Pathol 171: 1705–1712.
44. Hattori Y, Suzuki M, Hattori S, Kasai K (2003). Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia 46: 1543–1549.
45. Higgins LS, Mantzoros CS (2008). The development of INT131 as a selective PPARgamma modulator: approach to a safer insulin sensitizer. PPAR Res 2008: 936906.
46. Hiramatsu-Ito M, Shibata R, Ohashi K, Uemura Y, Kanemura N, Kambara T et al. (2016). Omentin attenuates atherosclerotic lesion formation in apolipoprotein E-deficient mice. Cardiovasc Res 110: 107–117.
47. Hirata Y, Tabata M, Kurobe H, Motoki T, Akaike M, Nishio C et al. (2011). Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue. J Am Coll Cardiol 58: 248–255.
48. Hirata Y, Yamada H, Kusunose K, Iwase T, Nishio S, Hayashi S et al. (2015). Clinical utility of measuring epicardial adipose tissue thickness with echocardiography using a high-frequency linear probe in patients with coronary artery disease. J Am Soc Echocardiogr 28: 1240–1246.
49. Hoffmann A, Ebert T, Kloting N, Dokas J, Jeromin F, Jessnitzer B et al. (2016). Leptin dose-dependently decreases atherosclerosis by attenuation of hypercholesterolemia and induction of adiponectin. Biochim Biophys Acta 1862: 113–120.
50. Holland WL, Miller RA, Wang ZV, Sun K, Barth BM, Bui HH et al. (2011). Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med 17: 55–63.
51. Hong EG, Ko HJ, Cho YR, Kim HJ, Ma Z, Yu TY et al. (2009). Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes 58: 2525–2535.
52. Huber SA, Sakkinen P, Conze D, Hardin N, Tracy R (1999). Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscler Thromb Vasc Biol 19: 2364–2367.
53. Hung J, McQuillan BM, Thompson PL, Beilby JP (2008). Circulating adiponectin levels associate with inflammatory markers, insulin resistance and metabolic syndrome independent of obesity. Int J Obes (Lond) 32: 772–779.
54. Huypens P, Quartier E, Pipeleers D, Van de Casteele M (2005). Metformin reduces adiponectin protein expression and release in 3T3-L1 adipocytes involving activation of AMP activated protein kinase. Eur J Pharmacol 518: 90–95.
55. Iacobellis G (2015). Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol 11: 363–371.
56. Iacobellis G, Pistilli D, Gucciardo M, Leonetti F, Miraldi F, Brancaccio G et al. (2005). Adiponectin expression in human epicardial adipose tissue in vivo is lower in patients with coronary artery disease. Cytokine 29: 251–255.
57. Ibrahim MM (2010). Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 11: 11–18.
58. Iglseder B, Mackevics V, Stadlmayer A, Tasch G, Ladurner G, Paulweber B (2005). Plasma adiponectin levels and sonographic phenotypes of subclinical carotid artery atherosclerosis: data from the SAPHIR Study. Stroke 36: 2577–2582.
59. Jay D, Hitomi H, Griendling KK (2006). Oxidative stress and diabetic cardiovascular complications. Free Radic Biol Med 40: 183–192.
60. Johnson AM, Olefsky JM (2013). The origins and drivers of insulin resistance. Cell 152: 673–684.
61. Jung HS, Park KH, Cho YM, Chung SS, Cho HJ, Cho SY et al. (2006). Resistin is secreted from macrophages in atheromas and promotes atherosclerosis. Cardiovasc Res 69: 76–85.
62. Kadoglou NP, Lampropoulos S, Kapelouzou A, Gkontopoulos A, Theofilogiannakos EK, Fotiadis G et al. (2010). Serum levels of apelin and ghrelin in patients with acute coronary syndromes and established coronary artery disease--KOZANI STUDY. Transl Res 155: 238–246.
63. Kadowaki T, Yamauchi T (2005). Adiponectin and adiponectin receptors. Endocr Rev 26: 439–451.
64. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K (2006). Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116: 1784–1792.
65. Kajikawa Y, Ikeda M, Takemoto S, Tomoda J, Ohmaru N, Kusachi S (2011). Association of circulating levels of leptin and adiponectin with metabolic syndrome and coronary heart disease in patients with various coronary risk factors. Int Heart J 52: 17–22.
66. Kamigaki M, Sakaue S, Tsujino I, Ohira H, Ikeda D, Itoh N et al. (2006). Oxidative stress provokes atherogenic changes in adipokine gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun 339: 624–632.
67. Kato H, Kashiwagi H, Shiraga M, Tadokoro S, Kamae T, Ujiie H et al. (2006). Adiponectin acts as an endogenous antithrombotic factor. Arterioscler Thromb Vasc Biol 26: 224–230.
68. Kazama K, Usui T, Okada M, Hara Y, Yamawaki H (2012). Omentin plays an anti-inflammatory role through inhibition of TNF-alpha-induced superoxide production in vascular smooth muscle cells. Eur J Pharmacol 686: 116–123.
69. Kiess W, Petzold S, Topfer M, Garten A, Bluher S, Kapellen T et al. (2008). Adipocytes and adipose tissue. Best Pract Res Clin Endocrinol Metab 22: 135–153.
70. Kim Chung le T, Hosaka T, Yoshida M, Harada N, Sakaue H, Sakai T et al. (2009). Exendin-4, a GLP-1 receptor agonist, directly induces adiponectin expression through protein kinase A pathway and prevents inflammatory adipokine expression. Biochem Biophys Res Commun 390: 613–618.
71. Kojima S, Funahashi T, Otsuka F, Maruyoshi H, Yamashita T, Kajiwara I et al. (2007). Future adverse cardiac events can be predicted by persistently low plasma adiponectin concentrations in men and marked reductions of adiponectin in women after acute myocardial infarction. Atherosclerosis 194: 204–213.
72. Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R (2006). Visceral fat is an independent predictor of all-cause mortality in men. Obesity (Silver Spring) 14: 336–341.
73. Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K et al. (2004). Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 109: 2046–2049.
74. Laughlin GA, Barrett-Connor E, May S, Langenberg C (2007). Association of adiponectin with coronary heart disease and mortality: the Rancho Bernardo study. Am J Epidemiol 165: 164–174.
75. Lawlor DA, Davey Smith G, Ebrahim S, Thompson C, Sattar N (2005). Plasma adiponectin levels are associated with insulin resistance, but do not predict future risk of coronary heart disease in women. J Clin Endocrinol Metab 90: 5677–5683.
76. Lee MJ, Wu Y, Fried SK (2013). Adipose tissue heterogeneity: implication of depot differences in adipose tissue for obesity complications. Mol Aspects Med 34: 1–11.
77. Leeper NJ, Tedesco MM, Kojima Y, Schultz GM, Kundu RK, Ashley EA et al. (2009). Apelin prevents aortic aneurysm formation by inhibiting macrophage inflammation. Am J Physiol Heart Circ Physiol 296: H1329–H1335.
78. Li CJ, Sun HW, Zhu FL, Chen L, Rong YY, Zhang Y et al. (2007). Local adiponectin treatment reduces atherosclerotic plaque size in rabbits. J Endocrinol 193: 137–145.
79. Li L, Miao Z, Liu R, Yang M, Liu H, Yang G (2011). Liraglutide prevents hypoadiponectinemia-induced insulin resistance and alterations of gene expression involved in glucose and lipid metabolism. Mol Med 17: 1168–1178.
80. Libby P, Ridker PM, Maseri A (2002). Inflammation and atherosclerosis. Circulation 105: 1135–1143.
81. Lindsay RS, Resnick HE, Zhu J, Tun ML, Howard BV, Zhang Y et al. (2005). Adiponectin and coronary heart disease: the Strong Heart Study. Arterioscler Thromb Vasc Biol 25: e15–e16.
82. Lis I, Pilarski L, Bogdanski P (2015). Omentin - a newly-discovered adipocytokine in insulin resistance pathogenesis. Pol Merkur Lekarski 39: 56–60.
83. Maceyka M, Harikumar KB, Milstien S, Spiegel S (2012). Sphingosine-1-phosphate signaling and its role in disease. Trends Cell Biol 22: 50–60.
84. Mackevics V, Heid IM, Wagner SA, Cip P, Doppelmayr H, Lejnieks A et al. (2006). The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians. Eur J Hum Genet 14: 349–356.
85. Margaritis M, Antonopoulos AS, Digby J, Lee R, Reilly S, Coutinho P et al. (2013). Interactions between vascular wall and perivascular adipose tissue reveal novel roles for adiponectin in the regulation of endothelial nitric oxide synthase function in human vessels. Circulation 127: 2209–2221.
86. Matsuda M, Kawasaki F, Yamada K, Kanda Y, Saito M, Eto M et al. (2004). Impact of adiposity and plasma adipocytokines on diabetic angiopathies in Japanese Type 2 diabetic subjects. Diabet Med 21: 881–888.
87. McEntegart MB, Awede B, Petrie MC, Sattar N, Dunn FG, MacFarlane NG et al. (2007). Increase in serum adiponectin concentration in patients with heart failure and cachexia: relationship with leptin, other cytokines, and B-type natriuretic peptide. Eur Heart J 28: 829–835.
88. Melistas L, Mantzoros CS, Kontogianni M, Antonopoulou S, Ordovas JM, Yiannakouris N (2009). Association of the +45T > G and +276G > T polymorphisms in the adiponectin gene with insulin resistance in nondiabetic Greek women. Eur J Endocrinol 161: 845–852.
89. Metais C, Forcheron F, Abdallah P, Basset A, Del Carmine P, Bricca G et al. (2008). Adiponectin receptors: expression in Zucker diabetic rats and effects of fenofibrate and metformin. Metabolism 57: 946–953.
90. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014). Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20: 1126–1167.
91. Motoshima H, Wu X, Sinha MK, Hardy VE, Rosato EL, Barbot DJ et al. (2002). Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone. J Clin Endocrinol Metab 87: 5662–5667.
92. Nakamura Y, Shimada K, Fukuda D, Shimada Y, Ehara S, Hirose M et al. (2004). Implications of plasma concentrations of adiponectin in patients with coronary artery disease. Heart 90: 528–533.
93. Nishida K, Okada Y, Nawata M, Saito K, Tanaka Y (2008). Induction of hyperadiponectinemia following long-term treatment of patients with rheumatoid arthritis with infliximab (IFX), an anti-TNF-alpha antibody. Endocr J 55: 213–216.
94. Nour-Eldine W, Ghantous CM, Zibara K, Dib L, Issaa H, Itani HA et al. (2016). Adiponectin attenuates angiotensin II-induced vascular smooth muscle cell remodeling through nitric oxide and the RhoA/ROCK pathway. Front Pharmacol 7: 86.
95. Ohashi K, Parker JL, Ouchi N, Higuchi A, Vita JA, Gokce N et al. (2010). Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem 285: 6153–6160.
96. Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K et al. (2013). A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 503: 493–499.
97. Okada-Iwabu M, Iwabu M, Ueki K, Yamauchi T, Kadowaki T (2015). Perspective of small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Diabetes Metab J 39: 363–372.
98. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M et al. (2002). Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 106: 2767–2770.
99. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H et al. (2000). Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102: 1296–1301.
100. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y et al. (2001). Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 103: 1057–1063.
101. Ouchi N, Parker JL, Lugus JJ, Walsh K (2011). Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11: 85–97.
102. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG (2011). Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29: 71–109.
103. Paakko T, Ukkola O, Ikaheimo M, Kesaniemi YA (2010). Plasma adiponectin levels are associated with left ventricular hypertrophy in a random sample of middle-aged subjects. Ann Med 42: 131–137.
104. Pajvani UB, Du X, Combs TP, Berg AH, Rajala MW, Schulthess T et al. (2003). Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. implications fpr metabolic regulation and bioactivity. J Biol Chem 278: 9073–9085.
105. Patel SB, Reams GP, Spear RM, Freeman RH, Villarreal D (2008). Leptin: linking obesity, the metabolic syndrome, and cardiovascular disease. Curr Hypertens Rep 10: 131–137.
106. Phillips SA, Ciaraldi TP, Kong AP, Bandukwala R, Aroda V, Carter L et al. (2003). Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy. Diabetes 52: 667–674.
107. Pinderski LJ, Fischbein MP, Subbanagounder G, Fishbein MC, Kubo N, Cheroutre H et al. (2002). Overexpression of interleukin-10 by activated T lymphocytes inhibits atherosclerosis in LDL receptor-deficient Mice by altering lymphocyte and macrophage phenotypes. Circ Res 90: 1064–1071.
108. Resink TJ, Philippova M, Joshi MB, Kyriakakis E, Erne P (2009). Cadherins and cardiovascular disease. Swiss Med Wkly 139: 122–134.
109. Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E (2000). Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 101: 2149–2153.
110. Rotter V, Nagaev I, Smith U (2003). Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem 278: 45777–45784.
111. Ruan H, Dong LQ (2016). Adiponectin signaling and function in insulin target tissues. J Mol Cell Biol 8: 101–109.
112. Sahebkar A, Ponzo V, Bo S (2016). Effect of dipeptidyl peptidase-4 inhibitors on plasma adiponectin: a systematic review and meta-analysis of randomized controlled trials. Curr Med Chem 23: 1356–1369.
113. Saito K, Tobe T, Minoshima S, Asakawa S, Sumiya J, Yoda M et al. (1999). Organization of the gene for gelatin-binding protein (GBP28). Gene 229: 67–73.
114. Sattar N, Wannamethee G, Sarwar N, Tchernova J, Cherry L, Wallace AM et al. (2006). Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation 114: 623–629.
115. Schautz B, Later W, Heller M, Peters A, Muller MJ, Bosy-Westphal A (2012). Impact of age on leptin and adiponectin independent of adiposity. Br J Nutr 108: 363–370.
116. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (1995). A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270: 26746–26749.
117. Schulze MB, Shai I, Rimm EB, Li T, Rifai N, Hu FB (2005). Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 54: 534–539.
118. Scotece M, Conde J, Lopez V, Lago F, Pino J, Gomez-Reino JJ et al. (2014). Adiponectin and leptin: new targets in inflammation. Basic Clin Pharmacol Toxicol 114: 97–102.
119. Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR et al. (2004). Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 10: 1384–1389.
120. Shibata R, Sato K, Kumada M, Izumiya Y, Sonoda M, Kihara S et al. (2007). Adiponectin accumulates in myocardial tissue that has been damaged by ischemia-reperfusion injury via leakage from the vascular compartment. Cardiovasc Res 74: 471–479.
121. Shibata R, Ouchi N, Kikuchi R, Takahashi R, Takeshita K, Kataoka Y et al. (2011). Circulating omentin is associated with coronary artery disease in men. Atherosclerosis 219: 811–814.
122. Shin MJ, Jang Y, Koh SJ, Chae JS, Kim OY, Lee JE et al. (2006). The association of SNP276G > T at adiponectin gene with circulating adiponectin and insulin resistance in response to mild weight loss. Int J Obes (Lond) 30: 1702–1708.
123. Sook Lee E, Park SS, Kim E, Sook Yoon Y, Ahn HY, Park CY et al. (2013). Association between adiponectin levels and coronary heart disease and mortality: a systematic review and meta-analysis. Int J Epidemiol 42: 1029–1039.
124. Southan C, Sharman JL, Benson HE, Faccenda E, Pawson AJ, Alexander SP et al. (2016). The IUPHAR/BPS guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucleic Acids Res 44: D1054–D1068.
125. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM et al. (2001). The hormone resistin links obesity to diabetes. Nature 409: 307–312.
126. Stern JH, Scherer PE (2015). Adipose tissue biology in 2014: Advances in our understanding of adipose tissue homeostasis. Nat Rev Endocrinol 11: 71–72.
127. Tahara A, Takasu T, Yokono M, Imamura M, Kurosaki E (2016). Characterization and comparison of sodium-glucose cotransporter 2 inhibitors: Part 2. Antidiabetic effects in type 2 diabetic mice. J Pharmacol Sci 131: 198–208.
128. Tao L, Gao E, Jiao X, Yuan Y, Li S, Christopher TA et al. (2007). Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation 115: 1408–1416.
129. Than A, Zhang X, Leow MK, Poh CL, Chong SK, Chen P (2014). Apelin attenuates oxidative stress in human adipocytes. J Biol Chem 289: 3763–3774.
130. Tsuchida A, Yamauchi T, Ito Y, Hada Y, Maki T, Takekawa S et al. (2004). Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem 279: 30817–30822.
131. Tsukamoto O, Fujita M, Kato M, Yamazaki S, Asano Y, Ogai A et al. (2009). Natriuretic peptides enhance the production of adiponectin in human adipocytes and in patients with chronic heart failure. J Am Coll Cardiol 53: 2070–2077.
132. Tullin S, Sams A, Brandt J, Dahl K, Gong W, Jeppesen CB et al. (2012). Recombinant adiponectin does not lower plasma glucose in animal models of type 2 diabetes. PLoS One 7: e44270.
133. Turer AT, Scherer PE (2012). Adiponectin: mechanistic insights and clinical implications. Diabetologia 55: 2319–2326.
134. Van Berendoncks AM, Conraads VM (2011). Functional adiponectin resistance and exercise intolerance in heart failure. Curr Heart Fail Rep 8: 113–122.
135. Van Brocklyn JR, Williams JB (2012). The control of the balance between ceramide and sphingosine-1-phosphate by sphingosine kinase: oxidative stress and the seesaw of cell survival and death. Comp Biochem Physiol B Biochem Mol Biol 163: 26–36.
136. Venteclef N, Guglielmi V, Balse E, Gaborit B, Cotillard A, Atassi F et al. (2015). Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. Eur Heart J 36: 795–805a.
137. Wajchenberg BL (2000). Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21: 697–738.
138. Wang B, Jenkins JR, Trayhurn P (2005a). Expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture: integrated response to TNF-alpha. Am J Physiol Endocrinol Metab 288: E731–E740.
139. Wang Y, Lam KS, Xu JY, Lu G, Xu LY, Cooper GJ et al. (2005b). Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem 280: 18341–18347.
140. Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z et al. (2014). The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med 20: 1436–1443.
141. Wannamethee SG, Whincup PH, Lennon L, Sattar N (2007). Circulating adiponectin levels and mortality in elderly men with and without cardiovascular disease and heart failure. Arch Intern Med 167: 1510–1517.
142. Wannamethee SG, Welsh P, Whincup PH, Sawar N, Thomas MC, Gudnarsson V et al. (2011). High adiponectin and increased risk of cardiovascular disease and mortality in asymptomatic older men: does NT-proBNP help to explain this association? Eur J Cardiovasc Prev Rehabil 18: 65–71.
143. Watanabe S, Okura T, Kurata M, Irita J, Manabe S, Miyoshi K et al. (2006). The effect of losartan and amlodipine on serum adiponectin in Japanese adults with essential hypertension. Clin Ther 28: 1677–1685.
144. Welsh P, Murray HM, Ford I, Trompet S, de Craen AJ, Jukema JW et al. (2011). Circulating interleukin-10 and risk of cardiovascular events: a prospective study in the elderly at risk. Arterioscler Thromb Vasc Biol 31: 2338–2344.
145. Yadav A, Kataria MA, Saini V, Yadav A (2013). Role of leptin and adiponectin in insulin resistance. Clin Chim Acta 417: 80–84.
146. Yamaguchi N, Argueta JG, Masuhiro Y, Kagishita M, Nonaka K, Saito T et al. (2005). Adiponectin inhibits Toll-like receptor family-induced signaling. FEBS Lett 579: 6821–6826.
147. Yamauchi T, Kadowaki T (2008). Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases. Int J Obes (Lond) 32 (Suppl 7): S13–S18.
148. Yamauchi T, Kadowaki T (2013). Adiponectin receptor as a key player in healthy longevity and obesity-related diseases. Cell Metab 17: 185–196.
149. Yamauchi T, Iwabu M, Okada-Iwabu M, Kadowaki T (2014). Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab 28: 15–23.
150. Yamawaki H, Kuramoto J, Kameshima S, Usui T, Okada M, Hara Y (2011). Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells. Biochem Biophys Res Commun 408: 339–343.
151. Yan W, Zhang H, Liu P, Wang H, Liu J, Gao C et al. (2013). Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1alpha signaling contributing to increased vulnerability in diabetic heart. Basic Res Cardiol 108: 329.
152. Young ME, Guthrie PH, Razeghi P, Leighton B, Abbasi S, Patil S et al. (2002). Impaired long-chain fatty acid oxidation and contractile dysfunction in the obese Zucker rat heart. Diabetes 51: 2587–2595.
153. Yu JG, Javorschi S, Hevener AL, Kruszynska YT, Norman RA, Sinha M et al. (2002). The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 51: 2968–2974.
154. Yuan G, Jia J, Di L, Zhou L, Dong S, Ye J et al. (2012). Effects of C-reactive protein on adipokines genes expression in 3 T3-L1 adipocytes. Biochem Biophys Res Commun 424: 462–468.
155. Yue P, Jin H, Aillaud M, Deng AC, Azuma J, Asagami T et al. (2010). Apelin is necessary for the maintenance of insulin sensitivity. Am J Physiol Endocrinol Metab 298: E59–E67.
156. Zelova H, Hosek J (2013). TNF-alpha signalling and inflammation: interactions between old acquaintances. Inflamm Res 62: 641–651.
157. Zhang Y, Matheny M, Zolotukhin S, Tumer N, Scarpace PJ (2002). Regulation of adiponectin and leptin gene expression in white and brown adipose tissues: influence of beta3-adrenergic agonists, retinoic acid, leptin and fasting. Biochim Biophys Acta 1584: 115–122.
158. Zhou Y, Wang Y, Qiao S (2014). Apelin: a potential marker of coronary artery stenosis and atherosclerotic plaque stability in ACS patients. Int Heart J 55: 204–212.