Adiponectin, Obesity, and Cancer: Clash of the Bigwigs in Health and Disease

Sheetal Parida, Sumit Siddharth, Dipali Sharma, Sheetal Parida, Sumit Siddharth, Dipali Sharma

Abstract

Adiponectin is one of the most important adipocytokines secreted by adipocytes and is called a "guardian angel adipocytokine" owing to its unique biological functions. Adiponectin inversely correlates with body fat mass and visceral adiposity. Identified independently by four different research groups, adiponectin has multiple names; Acrp30, apM1, GBP28, and AdipoQ. Adiponectin mediates its biological functions via three known receptors, AdipoR1, AdipoR2, and T-cadherin, which are distributed throughout the body. Biological functions of adiponectin are multifold ranging from anti-diabetic, anti-atherogenic, anti-inflammatory to anti-cancer. Lower adiponectin levels have been associated with metabolic syndrome, type 2 diabetes, insulin resistance, cardiovascular diseases, and hypertension. A plethora of experimental evidence supports the role of obesity and increased adiposity in multiple cancers including breast, liver, pancreatic, prostrate, ovarian, and colorectal cancers. Obesity mediates its effect on cancer progression via dysregulation of adipocytokines including increased production of oncogenic adipokine leptin along with decreased production of adiponectin. Multiple studies have shown the protective role of adiponectin in obesity-associated diseases and cancer. Adiponectin modulates multiple signaling pathways to exert its physiological and protective functions. Many studies over the years have shown the beneficial effect of adiponectin in cancer regression and put forth various innovative ways to increase adiponectin levels.

Keywords: adiponectin; cancer; obesity.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Multiple signaling networks converge to regulate adiponectin.
Figure 2
Figure 2
Adiponectin modulates various signaling mechanisms to inhibit caner growth.

References

    1. Brochu-Gaudreau K., Rehfeldt C., Blouin R., Bordignon V., Murphy B.D., Palin M.-F. Adiponectin action from head to toe. Endocrine. 2010;37:11–32. doi: 10.1007/s12020-009-9278-8.
    1. Wang G.-X., Zhao X.-Y., Lin J.D. The brown fat secretome: Metabolic functions beyond thermogenesis. Trends Endocrinol. Metab. TEM. 2015;26:231–237. doi: 10.1016/j.tem.2015.03.002.
    1. Scherer P.E., Williams S., Fogliano M., Baldini G., Lodish H.F. A novel serum protein similar to C1q, produced exclusively in adipocytes. J. Biol. Chem. 1995;270:26746–26749. doi: 10.1074/jbc.270.45.26746.
    1. Hu E., Liang P., Spiegelman B.M. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 1996;271:10697–10703. doi: 10.1074/jbc.271.18.10697.
    1. Maeda K., Okubo K., Shimomura I., Funahashi T., Matsuzawa Y., Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1) Biochem. Biophys. Res. Commun. 1996;221:286–289. doi: 10.1006/bbrc.1996.0587.
    1. Nakano Y., Tobe T., Choi-Miura N.H., Mazda T., Tomita M. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J. Biochem. 1996;120:803–812. doi: 10.1093/oxfordjournals.jbchem.a021483.
    1. Berg A.H., Combs T.P., Du X., Brownlee M., Scherer P.E. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat. Med. 2001;7:947–953. doi: 10.1038/90992.
    1. Yamauchi T., Kamon J., Waki H., Terauchi Y., Kubota N., Hara K., Mori Y., Ide T., Murakami K., Tsuboyama-Kasaoka N., et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 2001;7:941–946. doi: 10.1038/90984.
    1. Combs T.P., Berg A.H., Obici S., Scherer P.E., Rossetti L. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J. Clin. Investig. 2001;108:1875–1881. doi: 10.1172/JCI14120.
    1. Yamauchi T., Kamon J., Minokoshi Y., Ito Y., Waki H., Uchida S., Yamashita S., Noda M., Kita S., Ueki K., et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 2002;8:1288–1295. doi: 10.1038/nm788.
    1. Qi Y., Takahashi N., Hileman S.M., Patel H.R., Berg A.H., Pajvani U.B., Scherer P.E., Ahima R.S. Adiponectin acts in the brain to decrease body weight. Nat. Med. 2004;10:524–529. doi: 10.1038/nm1029.
    1. Holland W.L., Miller R.A., Wang Z.V., Sun K., Barth B.M., Bui H.H., Davis K.E., Bikman B.T., Halberg N., Rutkowski J.M., et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat. Med. 2011;17:55–63. doi: 10.1038/nm.2277.
    1. Chaurasia B., Summers S.A. Ceramides—Lipotoxic Inducers of Metabolic Disorders. Trends Endocrinol. Metab. 2015;26:538–550. doi: 10.1016/j.tem.2015.07.006.
    1. Xia J.Y., Holland W.L., Kusminski C.M., Sun K., Sharma A.X., Pearson M.J., Sifuentes A.J., McDonald J.G., Gordillo R., Scherer P.E. Targeted Induction of Ceramide Degradation Leads to Improved Systemic Metabolism and Reduced Hepatic Steatosis. Cell Metab. 2015;22:266–278. doi: 10.1016/j.cmet.2015.06.007.
    1. Rutkowski J.M., Wang Z.V., Park A.S., Zhang J., Zhang D., Hu M.C., Moe O.W., Susztak K., Scherer P.E. Adiponectin promotes functional recovery after podocyte ablation. J. Am. Soc. Nephrol. 2013;24:268–282. doi: 10.1681/ASN.2012040414.
    1. Dadson K., Turdi S., Hashemi S., Zhao J., Polidovitch N., Beca S., Backx P.H., McDermott J.C., Sweeney G. Adiponectin is required for cardiac MEF2 activation during pressure overload induced hypertrophy. J. Mol. Cell Cardiol. 2015;86:102–109. doi: 10.1016/j.yjmcc.2015.06.020.
    1. Kadowaki T., Yamauchi T. Adiponectin and adiponectin receptors. Endocr. Rev. 2005;26:439–451. doi: 10.1210/er.2005-0005.
    1. Hug C., Wang J., Ahmad N.S., Bogan J.S., Tsao T.S., Lodish H.F. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc. Natl. Acad. Sci. USA. 2004;101:10308–10313. doi: 10.1073/pnas.0403382101.
    1. Iwaki M., Matsuda M., Maeda N., Funahashi T., Matsuzawa Y., Makishima M., Shimomura I. Induction of Adiponectin, a Fat-Derived Antidiabetic and Antiatherogenic Factor, by Nuclear Receptors. Diabetes. 2003;52:1655–1663. doi: 10.2337/diabetes.52.7.1655.
    1. Yu J.G., Javorschi S., Hevener A.L., Kruszynska Y.T., Norman R.A., Sinha M., Olefsky J.M. The Effect of Thiazolidinediones on Plasma Adiponectin Levels in Normal, Obese, and Type 2 Diabetic Subjects. Diabetes. 2002;51:2968–2974. doi: 10.2337/diabetes.51.10.2968.
    1. Kanatani Y., Usui I., Ishizuka K., Bukhari A., Fujisaka S., Urakaze M., Haruta T., Kishimoto T., Naka T., Kobayashi M. Effects of Pioglitazone on Suppressor of Cytokine Signaling 3 Expression. Potential Mech. Its Eff. Insul. Sensit. Adiponectin Expr. 2007;56:795–803.
    1. Nakae J., Kitamura T., Kitamura Y., Biggs W.H., Arden K.C., Accili D. The Forkhead Transcription Factor Foxo1 Regulates Adipocyte Differentiation. Dev. Cell. 2003;4:119–129. doi: 10.1016/S1534-5807(02)00401-X.
    1. Qiao L., Shao J. SIRT1 Regulates Adiponectin Gene Expression through Foxo1-C/Enhancer-binding Protein α Transcriptional Complex. J. Biol. Chem. 2006;281:39915–39924. doi: 10.1074/jbc.M607215200.
    1. Park B.-H., Qiang L., Farmer S.R. Phosphorylation of C/EBPβ at a Consensus Extracellular Signal-Regulated Kinase/Glycogen Synthase Kinase 3 Site Is Required for the Induction of Adiponectin Gene Expression during the Differentiation of Mouse Fibroblasts into Adipocytes. Mol. Cell. Biol. 2004;24:8671–8680. doi: 10.1128/MCB.24.19.8671-8680.2004.
    1. Gustafson B., Jack M.M., Cushman S.W., Smith U. Adiponectin gene activation by thiazolidinediones requires PPARγ2, but not C/EBPα—Evidence for differential regulation of the aP2 and adiponectin genes. Biochem. Biophys. Res. Commun. 2003;308:933–939. doi: 10.1016/S0006-291X(03)01518-3.
    1. Seo J.B., Moon H.M., Noh M.J., Lee Y.S., Jeong H.W., Yoo E.J., Kim W.S., Park J., Youn B.-S., Kim J.W., et al. Adipocyte Determination- and Differentiation-dependent Factor 1/Sterol Regulatory Element-binding Protein 1c Regulates Mouse Adiponectin Expression. J. Biol. Chem. 2004;279:22108–22117. doi: 10.1074/jbc.M400238200.
    1. Zhang J.-W., Klemm D.J., Vinson C., Lane M.D. Role of CREB in Transcriptional Regulation of CCAAT/Enhancer-binding Protein β Gene during Adipogenesis. J. Biol. Chem. 2004;279:4471–4478. doi: 10.1074/jbc.M311327200.
    1. Kim H.B., Kong M., Kim T.M., Suh Y.H., Kim W.-H., Lim J.H., Song J.H., Jung M.H. NFATc4 and ATF3 Negatively Regulate Adiponectin Gene Expression in 3T3-L1 Adipocytes. Diabetes. 2006;55:1342–1352. doi: 10.2337/db05-1507.
    1. Ho I.-C., Kim J.H.-J., Rooney J.W., Spiegelman B.M., Glimcher L.H. A potential role for the nuclear factor of activated T cells family of transcriptional regulatory proteins in adipogenesis. Proc. Natl. Acad. Sci. USA. 1998;95:15537–15541. doi: 10.1073/pnas.95.26.15537.
    1. Liu M., Liu F. Transcriptional and post-translational regulation of adiponectin. Biochem. J. 2010;425:41–52. doi: 10.1042/BJ20091045.
    1. Lim J.-Y., Kim W.H., Park S.I. GO6976 prevents TNF-α-induced suppression of adiponectin expression in 3T3-L1 adipocytes: Putative involvement of protein kinase C. FEBS Lett. 2008;582:3473–3478. doi: 10.1016/j.febslet.2008.09.012.
    1. Zappalà G., Rechler M.M. IGFBP-3, hypoxia and TNF-α inhibit adiponectin transcription. Biochem. Biophys. Res. Commun. 2009;382:785–789. doi: 10.1016/j.bbrc.2009.03.112.
    1. Fasshauer M., Kralisch S., Klier M., Lossner U., Bluher M., Klein J., Paschke R. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 2003;301:1045–1050. doi: 10.1016/S0006-291X(03)00090-1.
    1. Kusminski C.M., McTernan P.G., Schraw T., Kos K., O’Hare J.P., Ahima R., Kumar S., Scherer P.E. Adiponectin complexes in human cerebrospinal fluid: Distinct complex distribution from serum. Diabetologia. 2007;50:634–642. doi: 10.1007/s00125-006-0577-9.
    1. Kadowaki T., Yamauchi T., Kubota N., Hara K., Ueki K., Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Investig. 2006;116:1784–1792. doi: 10.1172/JCI29126.
    1. Phillips S.A., Kung J.T. Mechanisms of adiponectin regulation and use as a pharmacological target. Curr. Opin. Pharmacol. 2010;10:676–683. doi: 10.1016/j.coph.2010.08.002.
    1. Berg A.H., Combs T.P., Scherer P.E. ACRP30/adiponectin: An adipokine regulating glucose and lipid metabolism. Trends Endocrinol. Metab. 2002;13:84–89. doi: 10.1016/S1043-2760(01)00524-0.
    1. Wang Y., Lam K.S.L., Chan L., Chan K.W., Lam J.B.B., Lam M.C., Hoo R.C.L., Mak W.W.N., Cooper G.J.S., Xu A. Post-translational Modifications of the Four Conserved Lysine Residues within the Collagenous Domain of Adiponectin Are Required for the Formation of Its High Molecular Weight Oligomeric Complex. J. Biol. Chem. 2006;281:16391–16400. doi: 10.1074/jbc.M513907200.
    1. Richards A.A., Macdonald G.A., Charlton H.K., Prins J.B., Stephens T., Whitehead J.P., Jones A. Adiponectin Multimerization Is Dependent on Conserved Lysines in the Collagenous Domain: Evidence for Regulation of Multimerization by Alterations in Posttranslational Modifications. Mol. Endocrinol. 2006;20:1673–1687. doi: 10.1210/me.2005-0390.
    1. Wang Z.V., Schraw T.D., Kim J.-Y., Khan T., Rajala M.W., Follenzi A., Scherer P.E. Secretion of the Adipocyte-Specific Secretory Protein Adiponectin Critically Depends on Thiol-Mediated Protein Retention. Mol. Cell. Biol. 2007;27:3716–3731. doi: 10.1128/MCB.00931-06.
    1. Qiang L., Wang H., Farmer S.R. Adiponectin Secretion Is Regulated by SIRT1 and the Endoplasmic Reticulum Oxidoreductase Ero1-Lα. Mol. Cell. Biol. 2007;27:4698–4707. doi: 10.1128/MCB.02279-06.
    1. Phillips S.A., Kung J., Ciaraldi T.P., Choe C., Christiansen L., Mudaliar S., Henry R.R. Selective regulation of cellular and secreted multimeric adiponectin by antidiabetic therapies in humans. Am. J. Physiol. Endocrinol. Metab. 2009;297:E767–E773. doi: 10.1152/ajpendo.00378.2009.
    1. Liu M., Zhou L., Xu A., Lam K.S.L., Wetzel M.D., Xiang R., Zhang J., Xin X., Dong L.Q., Liu F. A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization. Proc. Natl. Acad. Sci. USA. 2008;105:18302–18307. doi: 10.1073/pnas.0806341105.
    1. Mitchell M., Armstrong D.T., Robker R.L., Norman R.J. Adipokines: Implications for female fertility and obesity. Reproduction. 2005;130:583. doi: 10.1530/rep.1.00521.
    1. Chabrolle C., Tosca L., Dupont J.L. Regulation of adiponectin and its receptors in rat ovary by human chorionic gonadotrophin treatment and potential involvement of adiponectin in granulosa cell steroidogenesis. Reproduction. 2007;133:719. doi: 10.1530/REP-06-0244.
    1. Leff T. AMP-activated protein kinase regulates gene expression by direct phosphorylation of nuclear proteins. Biochem. Soc. Trans. 2003;31:224–227. doi: 10.1042/bst0310224.
    1. Dupont J., Chabrolle C., Ramé C., Tosca L., Coyral-Castel S. Role of the peroxisome proliferator-activated receptors, adenosine monophosphate-activated kinase, and adiponectin in the ovary. Ppar Res. 2008;2008:176275. doi: 10.1155/2008/176275.
    1. Archanco M., Gómez-Ambrosi J., Tena-Sempere M., Frühbeck G., Burrell M.A. Expression of Leptin and Adiponectin in the Rat Oviduct. J. Histochem. Cytochem. 2007;55:1027–1037. doi: 10.1369/jhc.6A7128.2007.
    1. Morimoto C., Koga K., Harada M., Yoshino O., Hirata T., Hirota Y., Taketani Y., Takemura Y., Osuga Y., Yano T., et al. Expression of Adiponectin Receptors and Its Possible Implication in the Human Endometrium. Endocrinology. 2006;147:3203–3210.
    1. Breitfeld J., Stumvoll M., Kovacs P. Genetics of adiponectin. Biochimie. 2012;94:2157–2163. doi: 10.1016/j.biochi.2012.03.004.
    1. Tokushige K., Hashimoto E., Noto H., Yatsuji S., Taniai M., Torii N., Shiratori K. Influence of adiponectin gene polymorphisms in Japanese patients with non-alcoholic fatty liver disease. J. Gastroenterol. 2009;44:976–982. doi: 10.1007/s00535-009-0085-z.
    1. Yoon M.J., Lee G.Y., Chung J.-J., Ahn Y.H., Hong S.H., Kim J.B. Adiponectin Increases Fatty Acid Oxidation in Skeletal Muscle Cells by Sequential Activation of AMP-Activated Protein Kinase, p38 Mitogen-Activated Protein Kinase, and Peroxisome Proliferator–Activated Receptor α. Diabetes. 2006;55:2562–2570. doi: 10.2337/db05-1322.
    1. Tomas E., Tsao T.-S., Saha A.K., Murrey H.E., Zhang C.c., Itani S.I., Lodish H.F., Ruderman N.B. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: Acetyl–CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc. Natl. Acad. Sci. USA. 2002;99:16309–16313. doi: 10.1073/pnas.222657499.
    1. Ceddia R.B., Somwar R., Maida A., Fang X., Bikopoulos G., Sweeney G. Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells. Diabetologia. 2005;48:132–139. doi: 10.1007/s00125-004-1609-y.
    1. Fang X., Palanivel R., Zhou X., Liu Y., Xu A., Wang Y., Sweeney G. Hyperglycemia- and hyperinsulinemia-induced alteration of adiponectin receptor expression and adiponectin effects in L6 myoblasts. J. Mol. Endocrinol. 2005;35:465–476. doi: 10.1677/jme.1.01877.
    1. Tsuchida A., Yamauchi T., Ito Y., Hada Y., Maki T., Takekawa S., Kamon J., Kobayashi M., Suzuki R., Hara K., et al. Insulin/Foxo1 Pathway Regulates Expression Levels of Adiponectin Receptors and Adiponectin Sensitivity. J. Biol. Chem. 2004;279:30817–30822. doi: 10.1074/jbc.M402367200.
    1. Kharroubi I., Rasschaert J., Eizirik D.L., Cnop M. Expression of adiponectin receptors in pancreatic β cells. Biochem. Biophys. Res. Commun. 2003;312:1118–1122. doi: 10.1016/j.bbrc.2003.11.042.
    1. Gu W., Li X., Liu C., Yang J., Ye L., Tang J., Gu Y., Yang Y., Hong J., Zhang Y., et al. Globular adiponectin augments insulin secretion from pancreatic Islet β cells at high glucose concentrations. Endocrine. 2006;30:217–221. doi: 10.1385/ENDO:30:2:217.
    1. Okamoto M., Ohara-Imaizumi M., Kubota N., Hashimoto S., Eto K., Kanno T., Kubota T., Wakui M., Nagai R., Noda M., et al. Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration. Diabetologia. 2008;51:827–835. doi: 10.1007/s00125-008-0944-9.
    1. Zyromski N.J., Mathur A., Pitt H.A., Wade T.E., Wang S., Swartz-Basile D.A., Prather A.D., Lillemoe K.D. Cannabinoid Receptor-1 Blockade Attenuates Acute pancreatitis in Obesity by An adiponectin Mediated Mechanism. J. Gastrointest. Surg. 2009;13:831. doi: 10.1007/s11605-009-0824-8.
    1. Bloemer J., Pinky P.D., Govindarajulu M., Hong H., Judd R., Amin R.H., Moore T., Dhanasekaran M., Reed M.N., Suppiramaniam V. Role of Adiponectin in Central Nervous System Disorders. Neural Plast. 2018;2018:4593530. doi: 10.1155/2018/4593530.
    1. Martinez-Fuentes A.J., Rodriguez-Pacheco F., Castaño J.P., Pinilla L., Tena-Sempere M., Malagon M.a.M., Dieguez C., Tovar S. Regulation of Pituitary Cell Function by Adiponectin. Endocrinology. 2007;148:401–410.
    1. Nishimura M., Izumiya Y., Higuchi A., Shibata R., Qiu J., Kudo C., Shin H.K., Moskowitz M.A., Ouchi N. Adiponectin Prevents Cerebral Ischemic Injury Through Endothelial Nitric Oxide Synthase–Dependent Mechanisms. Circulation. 2008;117:216–223. doi: 10.1161/CIRCULATIONAHA.107.725044.
    1. Neumeier M., Weigert J., Schäffler A., Wehrwein G., Müller-Ladner U., Schölmerich J., Wrede C., Buechler C. Different effects of adiponectin isoforms in human monocytic cells. J. Leukoc. Biol. 2006;79:803–808. doi: 10.1189/jlb.0905521.
    1. Wulster-Radcliffe M.C., Ajuwon K.M., Wang J., Christian J.A., Spurlock M.E. Adiponectin differentially regulates cytokines in porcine macrophages. Biochem. Biophys. Res. Commun. 2004;316:924–929. doi: 10.1016/j.bbrc.2004.02.130.
    1. Wolf A.M., Wolf D., Rumpold H., Enrich B., Tilg H. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem. Biophys. Res. Commun. 2004;323:630–635. doi: 10.1016/j.bbrc.2004.08.145.
    1. Šenolt L., Pavelka K., Housa D., Haluzík M. Increased adiponectin is negatively linked to the local inflammatory process in patients with rheumatoid arthritis. Cytokine. 2006;35:247–252. doi: 10.1016/j.cyto.2006.09.002.
    1. Ebina K., Fukuhara A., Ando W., Hirao M., Koga T., Oshima K., Matsuda M., Maeda K., Nakamura T., Ochi T., et al. Serum adiponectin concentrations correlate with severity of rheumatoid arthritis evaluated by extent of joint destruction. Clin. Rheumatol. 2009;28:445–451. doi: 10.1007/s10067-008-1074-y.
    1. Ehling A., Schäffler A., Herfarth H., Tarner I.H., Anders S., Distler O., Paul G., Distler J., Gay S., Schölmerich J., et al. The Potential of Adiponectin in Driving Arthritis. J. Immunol. 2006;176:4468–4478. doi: 10.4049/jimmunol.176.7.4468.
    1. Nakamura T., Tokunaga K., Shimomura I., Nishida M., Yoshida S., Kotani K., Islam A.H.M.W., Keno Y., Kobatake T., Nagai Y., et al. Contribution of visceral fat accumulation to the development of coronary artery disease in non-obese men. Atherosclerosis. 1994;107:239–246. doi: 10.1016/0021-9150(94)90025-6.
    1. Kobayashi H., Ouchi N., Kihara S., Walsh K., Kumada M., Abe Y., Funahashi T., Matsuzawa Y. Selective Suppression of Endothelial Cell Apoptosis by the High Molecular Weight Form of Adiponectin. Circ. Res. 2004;94:e27–e31. doi: 10.1161/01.RES.0000119921.86460.37.
    1. Otsuka F., Sugiyama S., Kojima S., Maruyoshi H., Funahashi T., Matsui K., Sakamoto T., Yoshimura M., Kimura K., Umemura S., et al. Plasma Adiponectin Levels Are Associated with Coronary Lesion Complexity in Men with Coronary Artery Disease. J. Am. Coll. Cardiol. 2006;48:1155–1162. doi: 10.1016/j.jacc.2006.05.054.
    1. Shibata R., Sato K., Pimentel D.R., Takemura Y., Kihara S., Ohashi K., Funahashi T., Ouchi N., Walsh K. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2–dependent mechanisms. Nat. Med. 2005;11:1096. doi: 10.1038/nm1295.
    1. Ikeda Y., Ohashi K., Shibata R., Pimentel D.R., Kihara S., Ouchi N., Walsh K. Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1 dependent mechanism in cardiac myocytes. FEBS Lett. 2008;582:1147–1150. doi: 10.1016/j.febslet.2008.03.002.
    1. Ouchi N., Kihara S., Arita Y., Maeda K., Kuriyama H., Okamoto Y., Hotta K., Nishida M., Takahashi M., Nakamura T., et al. Novel Modulator for Endothelial Adhesion Molecules. Circulation. 1999;100:2473–2476. doi: 10.1161/01.CIR.100.25.2473.
    1. Cnop M., Havel P.J., Utzschneider K.M., Carr D.B., Sinha M.K., Boyko E.J., Retzlaff B.M., Knopp R.H., Brunzell J.D., Kahn S.E. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: Evidence for independent roles of age and sex. Diabetologia. 2003;46:459–469. doi: 10.1007/s00125-003-1074-z.
    1. Rasmussen M.S., Lihn A.S., Pedersen S.B., Bruun J.M., Rasmussen M., Richelsen B. Adiponectin Receptors in Human Adipose Tissue: Effects of Obesity, Weight Loss, and Fat Depots. Obesity. 2006;14:28–35. doi: 10.1038/oby.2006.5.
    1. Spranger J., Kroke A., Möhlig M., Bergmann M.M., Ristow M., Boeing H., Pfeiffer A.F.H. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003;361:226–228. doi: 10.1016/S0140-6736(03)12255-6.
    1. Hara K., Horikoshi M., Yamauchi T., Yago H., Miyazaki O., Ebinuma H., Imai Y., Nagai R., Kadowaki T. Measurement of the High–Molecular Weight Form of Adiponectin in Plasma Is Useful for the Prediction of Insulin Resistance and Metabolic Syndrome. Diabetes Care. 2006;29:1357–1362. doi: 10.2337/dc05-1801.
    1. Ruchat S.-M., Loos R.J.F., Rankinen T., Vohl M.-C., Weisnagel S.J., Després J.-P., Bouchard C., Pérusse L. Associations between glucose tolerance, insulin sensitivity and insulin secretion phenotypes and polymorphisms in adiponectin and adiponectin receptor genes in the Quebec Family Study. Diabet. Med. 2008;25:400–406. doi: 10.1111/j.1464-5491.2008.02396.x.
    1. Wang Z.V., Scherer P.E. Adiponectin, Cardiovascular Function, and Hypertension. Hypertension. 2008;51:8–14. doi: 10.1161/HYPERTENSIONAHA.107.099424.
    1. Kurukulasuriya L.R., Stas S., Lastra G., Manrique C., Sowers J.R. Hypertension in Obesity. Endocrinol. Metab. Clin. N. Am. 2008;37:647–662. doi: 10.1016/j.ecl.2008.06.002.
    1. Kantartzis K., Rittig K., Balletshofer B., Machann J., Schick F., Porubska K., Fritsche A., Häring H.-U., Stefan N. The Relationships of Plasma Adiponectin with a Favorable Lipid Profile, Decreased Inflammation, and Less Ectopic Fat Accumulation Depend on Adiposity. Clin. Chem. 2006;52:1934–1942. doi: 10.1373/clinchem.2006.067397.
    1. Okada T., Saito E., Kuromori Y., Miyashita M., Iwata F., Hara M., Harada K. Relationship between serum adiponectin level and lipid composition in each lipoprotein fraction in adolescent children. Atherosclerosis. 2006;188:179–183. doi: 10.1016/j.atherosclerosis.2005.10.030.
    1. Vergès B., Petit J.M., Duvillard L., Dautin G., Florentin E., Galland F., Gambert P. Adiponectin Is an Important Determinant of ApoA-I Catabolism. Arteriosclerosis. Thrombosis. Vasc. Biol. 2006;26:1364–1369. doi: 10.1161/.
    1. Seino Y., Hirose H., Saito I., Itoh H. High-molecular-weight adiponectin is a predictor of progression to metabolic syndrome: A population-based 6-year follow-up study in Japanese men. Metabolism. 2009;58:355–360. doi: 10.1016/j.metabol.2008.10.008.
    1. Lara-Castro C., Luo N., Wallace P., Klein R.L., Garvey W.T. Adiponectin Multimeric Complexes and the Metabolic Syndrome Trait Cluster. Diabetes. 2006;55:249–259. doi: 10.2337/diabetes.55.01.06.db05-1105.
    1. Demirci H., Nuhoglu C., Ursavas I.S., Isildak S., Basaran E.O., Kilic M.Y. Obesity and asymptomatic hypertension among children aged 6–13 years living in Bursa, Turkey. Fam. Pr. 2013;30:629–633. doi: 10.1093/fampra/cmt048.
    1. Kim N.H., Cho N.H., Yun C.H., Lee S.K., Yoon D.W., Cho H.J., Ahn J.H., Seo J.A., Kim S.G., Choi K.M., et al. Association of obstructive sleep apnea and glucose metabolism in subjects with or without obesity. Diabetes Care. 2013;36:3909–3915. doi: 10.2337/dc13-0375.
    1. Ouchi N., Kihara S., Funahashi T., Matsuzawa Y., Walsh K. Obesity, adiponectin and vascular inflammatory disease. Curr. Opin. Lipidol. 2003;14:561–566. doi: 10.1097/00041433-200312000-00003.
    1. Iwashima Y., Katsuya T., Ishikawa K., Ouchi N., Ohishi M., Sugimoto K., Fu Y., Motone M., Yamamoto K., Matsuo A., et al. Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension. 2004;43:1318–1323. doi: 10.1161/01.HYP.0000129281.03801.4b.
    1. di Chiara T., Licata A., Argano C., Duro G., Corrao S., Scaglione R. Plasma adiponectin: A contributing factor for cardiac changes in visceral obesity-associated hypertension. Blood Press. 2014;23:147–153. doi: 10.3109/08037051.2013.823767.
    1. Ouchi N., Kihara S., Arita Y., Nishida M., Matsuyama A., Okamoto Y., Ishigami M., Kuriyama H., Kishida K., Nishizawa H., et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation. 2001;103:1057–1063. doi: 10.1161/01.CIR.103.8.1057.
    1. Avogaro A., de Kreutzenberg S.V. Mechanisms of endothelial dysfunction in obesity. Clin. Chim. Acta. 2005;360:9–26. doi: 10.1016/j.cccn.2005.04.020.
    1. Shimamoto Y., Mizukoshi M., Kuroi A., Imanishi T., Takeshita T., Terada M., Akasaka T. Is visceral fat really a coronary risk factor? A multi-detector computed tomography study. Int. Heart J. 2013;54:273–278. doi: 10.1536/ihj.54.273.
    1. Choi S.H., Hong E.S., Lim S. Clinical implications of adipocytokines and newly emerging metabolic factors with relation to insulin resistance and cardiovascular health. Front. Endocrinol. 2013;4:97. doi: 10.3389/fendo.2013.00097.
    1. Rega-Kaun G., Kaun C., Wojta J. More than a simple storage organ: Adipose tissue as a source of adipokines involved in cardiovascular disease. Thromb. Haemost. 2013;110:641–650. doi: 10.1160/TH13-03-0212.
    1. Diaz-Melean C.M., Somers V.K., Rodriguez-Escudero J.P., Singh P., Sochor O., Llano E.M., Lopez-Jimenez F. Mechanisms of adverse cardiometabolic consequences of obesity. Curr. Atheroscler Rep. 2013;15:364. doi: 10.1007/s11883-013-0364-2.
    1. Villarreal-Molina M.T., Antuna-Puente B. Adiponectin: Anti-inflammatory and cardioprotective effects. Biochimie. 2012;94:2143–2149. doi: 10.1016/j.biochi.2012.06.030.
    1. Matsuda M., Shimomura I. Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Rev. Endocr. Metab. Disord. 2014;15:1–10. doi: 10.1007/s11154-013-9271-7.
    1. Matsuda M., Shimomura I., Sata M., Arita Y., Nishida M., Maeda N., Kumada M., Okamoto Y., Nagaretani H., Nishizawa H., et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J. Biol. Chem. 2002;277:37487–37491. doi: 10.1074/jbc.M206083200.
    1. Ouchi N., Walsh K. Cardiovascular and metabolic regulation by the adiponectin/C1q/tumor necrosis factor-related protein family of proteins. Circulation. 2012;125:3066–3068. doi: 10.1161/CIRCULATIONAHA.112.114181.
    1. Mathew J.L., Narang I. Sleeping too close together: Obesity and obstructive sleep apnea in childhood and adolescence. Paediatr. Respir Rev. 2014;15:211–218. doi: 10.1016/j.prrv.2013.09.001.
    1. Hargens T.A., Guill S.G., Kaleth A.S., Nickols-Richardson S.M., Miller L.E., Zedalis D., Gregg J.M., Gwazdauskas F., Herbert W.G. Insulin resistance and adipose-derived hormones in young men with untreated obstructive sleep apnea. Sleep Breath. 2013;17:403–409. doi: 10.1007/s11325-012-0708-0.
    1. Nakagawa Y., Kishida K., Kihara S., Yoshida R., Funahashi T., Shimomura I. Nocturnal falls of adiponectin levels in sleep apnea with abdominal obesity and impact of hypoxia-induced dysregulated adiponectin production in obese murine mesenteric adipose tissue. J. Atheroscler. Thromb. 2011;18:240–247. doi: 10.5551/jat.6593.
    1. Magalang U.J., Cruff J.P., Rajappan R., Hunter M.G., Patel T., Marsh C.B., Raman S.V., Parinandi N.L. Intermittent hypoxia suppresses adiponectin secretion by adipocytes. Exp. Clin. Endocrinol. Diabetes. 2009;117:129–134. doi: 10.1055/s-2008-1078738.
    1. Klein B.E. Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol. 2007;14:179–183. doi: 10.1080/09286580701396720.
    1. Yilmaz M.I., Sonmez A., Acikel C., Celik T., Bingol N., Pinar M., Bayraktar Z., Ozata M. Adiponectin may play a part in the pathogenesis of diabetic retinopathy. Eur. J. Endocrinol. 2004;151:135–140. doi: 10.1530/eje.0.1510135.
    1. Vainio H., Bianchini F., editors. IARC Handbook of Cancer Prevention. Volume 6 IARC Press; Lyon, France: 2002.
    1. Iskander K., Farhour R., Ficek M., Ray A. Obesity-related complications: Few biochemical phenomena with reference to tumorigenesis. Malays. J. Pathol. 2013;35:1–15.
    1. Kwan M.L., John E.M., Caan B.J., Lee V.S., Bernstein L., Cheng I., Gomez S.L., Henderson B.E., Keegan T.H., Kurian A.W., et al. Obesity and mortality after breast cancer by race/ethnicity: The California Breast Cancer Survivorship Consortium. Am. J. Epidemiol. 2014;179:95–111. doi: 10.1093/aje/kwt233.
    1. Miyoshi Y., Funahashi T., Kihara S., Taguchi T., Tamaki Y., Matsuzawa Y., Noguchi S. Association of Serum Adiponectin Levels with Breast Cancer Risk. Clin. Cancer Res. 2003;9:5699–5704.
    1. Chen X., Wang Y. Adiponectin and breast cancer. Med. Oncol. 2011;28:1288–1295. doi: 10.1007/s12032-010-9617-x.
    1. Surmacz E. Leptin and adiponectin: Emerging therapeutic targets in breast cancer. J. Mammary Gland Biol. Neoplasia. 2013;18:321–332. doi: 10.1007/s10911-013-9302-8.
    1. Ohbuchi Y., Suzuki Y., Hatakeyama I., Nakao Y., Fujito A., Iwasaka T., Isaka K. A lower serum level of middle-molecular-weight adiponectin is a risk factor for endometrial cancer. Int. J. Clin. Oncol. 2014;19:667–673. doi: 10.1007/s10147-013-0603-0.
    1. Kerenidi T., Lada M., Tsaroucha A., Georgoulias P., Mystridou P., Gourgoulianis K.I. Clinical significance of serum adipokines levels in lung cancer. Med. Oncol. 2013;30:507. doi: 10.1007/s12032-013-0507-x.
    1. Kosova F., Coskun T., Kaya Y., Kara E., Ari Z. Adipocytokine levels of colon cancer patients before and after treatment. Bratisl. Lek. Listy. 2013;114:394–397. doi: 10.4149/BLL_2013_083.
    1. Liao L.M., Schwartz K., Pollak M., Graubard B.I., Li Z., Ruterbusch J., Rothman N., Davis F., Wacholder S., Colt J., et al. Serum leptin and adiponectin levels and risk of renal cell carcinoma. Obesity. 2013;21:1478–1485. doi: 10.1002/oby.20138.
    1. Wei T., Ye P., Peng X., Wu L.L., Yu G.Y. Circulating adiponectin levels in various malignancies: An updated meta-analysis of 107 studies. Oncotarget. 2016;7:48671–48691. doi: 10.18632/oncotarget.8932.
    1. Sun Y., Chen X. Effect of adiponectin on apoptosis: Proapoptosis or antiapoptosis? BioFactors. 2010;36:179–186. doi: 10.1002/biof.83.
    1. Fu S., Xu H., Liu C., Gu M., Wang Q., Zhou J., Wang Z. Role of adiponectin in prostate cancer: A preliminary study. Zhonghua Nan Ke Xue Natl. J. Androl. 2017;23:975–981.
    1. Gao Q., Zheng J., Yao X., Peng B. Adiponectin inhibits VEGF-A in prostate cancer cells. Tumor Biol. 2015;36:4287–4292. doi: 10.1007/s13277-015-3067-1.
    1. Shrestha A., Nepal S., Kim M.J., Chang J.H., Kim S.-H., Jeong G.-S., Jeong C.-H., Park G.H., Jung S., Lim J., et al. Critical Role of AMPK/FoxO3A Axis in Globular Adiponectin-Induced Cell Cycle Arrest and Apoptosis in Cancer Cells. J. Cell. Physiol. 2016;231:357–369. doi: 10.1002/jcp.25080.
    1. Xing S.-Q., Zhang C.-G., Yuan J.-F., Yang H.-M., Zhao S.-D., Zhang H. Adiponectin induces apoptosis in hepatocellular carcinoma through differential modulation of thioredoxin proteins. Biochem. Pharmacol. 2015;93:221–231. doi: 10.1016/j.bcp.2014.12.001.
    1. Otani K., Ishihara S., Yamaguchi H., Murono K., Yasuda K., Nishikawa T., Tanaka T., Kiyomatsu T., Hata K., Kawai K., et al. Adiponectin and colorectal cancer. Surg. Today. 2017;47:151–158. doi: 10.1007/s00595-016-1334-4.
    1. Fujisawa T., Endo H., Tomimoto A., Sugiyama M., Takahashi H., Saito S., Inamori M., Nakajima N., Watanabe M., Kubota N., et al. Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition. Gut. 2008;57:1531–1538. doi: 10.1136/gut.2008.159293.
    1. Moon H.-S., Liu X., Nagel J.M., Chamberland J.P., Diakopoulos K.N., Brinkoetter M.T., Hatziapostolou M., Wu Y., Robson S.C., Iliopoulos D., et al. Salutary effects of adiponectin on colon cancer: In vivo and in vitro studies in mice. Gut. 2013;62:561–570. doi: 10.1136/gutjnl-2012-302092.
    1. Bråkenhielm E., Veitonmäki N., Cao R., Kihara S., Matsuzawa Y., Zhivotovsky B., Funahashi T., Cao Y. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc. Natl. Acad. Sci. USA. 2004;101:2476–2481. doi: 10.1073/pnas.0308671100.
    1. Wang Y., Lam J.B., Lam K.S.L., Liu J., Lam M.C., Hoo R.L.C., Wu D., Cooper G.J.S., Xu A. Adiponectin Modulates the Glycogen Synthase Kinase-3β/β-Catenin Signaling Pathway and Attenuates Mammary Tumorigenesis of MDA-MB-231 Cells in Nude Mice. Cancer Res. 2006;66:11462–11470. doi: 10.1158/0008-5472.CAN-06-1969.
    1. Kang J.H., Lee Y.Y., Yu B.Y., Yang B.-S., Cho K.-H., Yoon D.K., Roh Y.K. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch. Pharmacal. Res. 2005;28:1263–1269. doi: 10.1007/BF02978210.
    1. Mutoh M., Teraoka N., Takasu S., Takahashi M., Onuma K., Yamamoto M., Kubota N., Iseki T., Kadowaki T., Sugimura T., et al. Loss of Adiponectin Promotes Intestinal Carcinogenesis in Min and Wild-type Mice. Gastroenterology. 2011;140:2000–2008.e2002. doi: 10.1053/j.gastro.2011.02.019.
    1. Saxena A., Chumanevich A., Fletcher E., Larsen B., Lattwein K., Kaur K., Fayad R. Adiponectin deficiency: Role in chronic inflammation induced colon cancer. Biochim. Biophys. Acta. 2012;1822:527–536. doi: 10.1016/j.bbadis.2011.12.006.
    1. Saxena A., Baliga M.S., Ponemone V., Kaur K., Larsen B., Fletcher E., Greene J., Fayad R. Mucus and adiponectin deficiency: Role in chronic inflammation-induced colon cancer. Int. J. Colorectal Dis. 2013;28:1267–1279. doi: 10.1007/s00384-013-1664-2.
    1. Kim A.Y., Lee Y.S., Kim K.H., Lee J.H., Lee H.K., Jang S.-H., Kim S.-E., Lee G.Y., Lee J.-W., Jung S.-A., et al. Adiponectin represses colon cancer cell proliferation via AdipoR1- and -R2-mediated AMPK activation. Mol. Endocrinol. 2010;24:1441–1452. doi: 10.1210/me.2009-0498.
    1. Guo X., Liu J., You L., Li G., Huang Y., Li Y. Association between adiponectin polymorphisms and the risk of colorectal cancer. Genet. Test. Mol. Biomark. 2015;19:9–13. doi: 10.1089/gtmb.2014.0238.
    1. Taliaferro-Smith L., Nagalingam A., Knight B.B., Oberlick E., Saxena N.K., Sharma D. Integral role of PTP1B in adiponectin-mediated inhibition of oncogenic actions of leptin in breast carcinogenesis. Neoplasia. 2013;15:23–38. doi: 10.1593/neo.121502.
    1. Wu X., Zhang Z., Du G., Wan X. Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells. Oncol. Rep. 2012;27:1488–1496.
    1. Man K., Ng K.T.P., Xu A., Cheng Q., Lo C.M., Xiao J.W., Sun B.S., Lim Z.X.H., Cheung J.S., Wu E.X., et al. Suppression of Liver Tumor Growth and Metastasis by Adiponectin in Nude Mice through Inhibition of Tumor Angiogenesis and Downregulation of Rho Kinase/IFN-Inducible Protein 10/Matrix Metalloproteinase 9 Signaling. Clin. Cancer Res. 2010;16:967–977. doi: 10.1158/1078-0432.CCR-09-1487.
    1. Cui E., Guo H., Shen M., Yu H., Gu D., Mao W., Wang X. Adiponectin inhibits migration and invasion by reversing epithelial-mesenchymal transition in non-small cell lung carcinoma. Oncol. Rep. 2018;40:1330–1338. doi: 10.3892/or.2018.6523.
    1. Taliaferro-Smith L., Nagalingam A., Zhong D., Zhou W., Saxena N.K., Sharma D. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and inhibition of migration and invasion of breast cancer cells. Oncogene. 2009;28:2621–2633. doi: 10.1038/onc.2009.129.
    1. Saxena N.K., Sharma D. Metastasis suppression by adiponectin: LKB1 rises up to the challenge. Cell Adh Migr. 2010;4:358–362. doi: 10.4161/cam.4.3.11541.
    1. Chung S.J., Nagaraju G.P., Nagalingam A., Muniraj N., Kuppusamy P., Walker A., Woo J., Gyorffy B., Gabrielson E., Saxena N.K., et al. ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through STK11/LKB1-mediated activation of the AMPK-ULK1 axis. Autophagy. 2017;13:1386–1403. doi: 10.1080/15548627.2017.1332565.
    1. Daniele A., de Rosa A., Nigro E., Scudiero O., Capasso M., Masullo M., de Laurentiis G., Oriani G., Sofia M., Bianco A. Adiponectin oligomerization state and adiponectin receptors airway expression in chronic obstructive pulmonary disease. Int. J. Biochem. Cell Biol. 2012;44:563–569. doi: 10.1016/j.biocel.2011.12.016.
    1. Cong L., Gasser J., Zhao J., Yang B., Li F., Zhao A.Z. Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2. Endocr. Relat. Cancer. 2007;14:713–720. doi: 10.1677/ERC-07-0065.
    1. Dieudonne M.N., Bussiere M., Santos E.D., Leneveu M.C., Giudicelli Y., Pecquery R. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem. Biophys. Res. Commun. 2006;345:271–279. doi: 10.1016/j.bbrc.2006.04.076.
    1. Davis R.J. Signal transduction by the JNK group of MAP kinases. Cell. 2000;103:239–252. doi: 10.1016/S0092-8674(00)00116-1.
    1. Hirosumi J., Tuncman G., Chang L., Gorgun C.Z., Uysal K.T., Maeda K., Karin M., Hotamisligil G.S. A central role for JNK in obesity and insulin resistance. Nature. 2002;420:333–336. doi: 10.1038/nature01137.
    1. Saxena N.K., Fu P.P., Nagalingam A., Wang J., Handy J., Cohen C., Tighiouart M., Sharma D., Anania F.A. Adiponectin modulates C-jun N-terminal kinase and mammalian target of rapamycin and inhibits hepatocellular carcinoma. Gastroenterology. 2010;139:1762–1773. doi: 10.1053/j.gastro.2010.07.001.
    1. Sharma D., Wang J., Fu P.P., Sharma S., Nagalingam A., Mells J., Handy J., Page A.J., Cohen C., Anania F.A., et al. Adiponectin antagonizes the oncogenic actions of leptin in hepatocellular carcinogenesis. Hepatology. 2010;52:1713–1722. doi: 10.1002/hep.23892.
    1. Vara J.A.F., Casado E., de Castro J., Cejas P., Belda-Iniesta C., Gonzalez-Baron M. PI3K/Akt signalling pathway and cancer. Cancer Treat. Rev. 2004;30:193–204. doi: 10.1016/j.ctrv.2003.07.007.
    1. Sugiyama M., Takahashi H., Hosono K., Endo H., Kato S., Yoneda K., Nozaki Y., Fujita K., Yoneda M., Wada K., et al. Adiponectin inhibits colorectal cancer cell growth through the AMPK/mTOR pathway. Int. J. Oncol. 2009;34:339–344.
    1. Liu J., Lam J.B., Chow K.H., Xu A., Lam K.S., Moon R.T., Wang Y. Adiponectin stimulates Wnt inhibitory factor-1 expression through epigenetic regulations involving the transcription factor specificity protein 1. Carcinogenesis. 2008;29:2195–2202. doi: 10.1093/carcin/bgn194.
    1. Ouchi N., Kihara S., Arita Y., Okamoto Y., Maeda K., Kuriyama H., Hotta K., Nishida M., Takahashi M., Muraguchi M., et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation. 2000;102:1296–1301. doi: 10.1161/01.CIR.102.11.1296.
    1. Wang Y., Xu A., Knight C., Xu L.Y., Cooper G.J.S. Hydroxylation and Glycosylation of the Four Conserved Lysine Residues in the Collagenous Domain of Adiponectin: POTENTIAL ROLE IN THE MODULATION OF ITS INSULIN-SENSITIZING ACTIVITY. J. Biol. Chem. 2002;277:19521–19529. doi: 10.1074/jbc.M200601200.
    1. Halberg N., Schraw T.D., Wang Z.V., Kim J.-Y., Yi J., Hamilton M.P., Luby-Phelps K., Scherer P.E. Systemic Fate of the Adipocyte-Derived Factor Adiponectin. Diabetes. 2009;58:1961–1970. doi: 10.2337/db08-1750.
    1. Das K., Lin Y., Widen E., Zhang Y., Scherer P.E. Chromosomal Localization, Expression Pattern, and Promoter Analysis of the Mouse Gene Encoding Adipocyte-Specific Secretory Protein Acrp30. Biochem. Biophys. Res. Commun. 2001;280:1120–1129. doi: 10.1006/bbrc.2001.4217.
    1. Kita A., Yamasaki H., Kuwahara H., Moriuchi A., Fukushima K., Kobayashi M., Fukushima T., Takahashi R., Abiru N., Uotani S., et al. Identification of the promoter region required for human adiponectin gene transcription: Association with CCAAT/enhancer binding protein-β and tumor necrosis factor-α. Biochem. Biophys. Res. Commun. 2005;331:484–490. doi: 10.1016/j.bbrc.2005.03.205.
    1. Kai T., Arima S., Taniyama Y., Nakabou M., Kanamasa K. Comparison of the Effect of Lipophilic and Hydrophilic Statins on Serum Adiponectin Levels in Patients with Mild Hypertension and Dyslipidemia: Kinki Adiponectin Interventional (KAI) Study. Clin. Exp. Hypertens. 2008;30:530–540. doi: 10.1080/10641960802251925.
    1. Hu Y., Tong G., Xu W., Pan J., Ryan K., Yang R., Shuldiner A.R., Gong D.-W., Zhu D. Anti-inflammatory effects of simvastatin on adipokines in type 2 diabetic patients with carotid atherosclerosis. Diabetes Vasc. Dis. Res. 2009;6:262–268. doi: 10.1177/1479164109339966.
    1. Tsutamoto T., Yamaji M., Kawahara C., Nishiyama K., Fujii M., Yamamoto T., Horie M. Effect of simvastatin vs. rosuvastatin on adiponectin and haemoglobin A1c levels in patients with non-ischaemic chronic heart failure. Eur. J. Heart Fail. 2009;11:1195–1201. doi: 10.1093/eurjhf/hfp144.
    1. Qu H.-Y., Xiao Y.-W., Jiang G.-H., Wang Z.-Y., Zhang Y., Zhang M. Effect of Atorvastatin Versus Rosuvastatin on Levels of Serum Lipids, Inflammatory Markers and Adiponectin in Patients with Hypercholesterolemia. Pharm. Res. 2009;26:958–964. doi: 10.1007/s11095-008-9798-6.
    1. Koh K.K., Quon M.J., Han S.H., Ahn J.Y., Jin D.K., Kim H.S., Kim D.S., Shin E.K. Vascular and Metabolic Effects of Combined Therapy with Ramipril and Simvastatin in Patients with Type 2 Diabetes. Hypertension. 2005;45:1088–1093. doi: 10.1161/.
    1. Nagamia S., Pandian A., Cheema F., Natarajan R., Khan Q.A., Patel A.D., Merchant N., Sola S., Khan B.V. The Role of Quinapril in the Presence of a Weight Loss Regimen: Endothelial Function and Markers of Obesity in Patients with the Metabolic Syndrome. Prev. Cardiol. 2007;10:204–209. doi: 10.1111/j.1520-037X.2007.06556.x.
    1. Koh K.K., Quon M.J., Han S.H., Chung W.-J., Ahn J.Y., Seo Y.-H., Kang M.H., Ahn T.H., Choi I.S., Shin E.K. Additive Beneficial Effects of Losartan Combined with Simvastatin in the Treatment of Hypercholesterolemic, Hypertensive Patients. Circulation. 2004;110:3687–3692. doi: 10.1161/01.CIR.0000143085.86697.13.
    1. Negro R., Formoso G., Hassan H. The effects of irbesartan and telmisartan on metabolic parameters and blood pressure in obese, insulin resistant, hypertensive patients. J. Endocrinol. Investig. 2006;29:957–961. doi: 10.1007/BF03349207.
    1. Furuhashi M., Ura N., Higashiura K., Murakami H., Tanaka M., Moniwa N., Yoshida D., Shimamoto K. Blockade of the Renin-Angiotensin System Increases Adiponectin Concentrations in Patients with Essential Hypertension. Hypertension. 2003;42:76–81. doi: 10.1161/01.HYP.0000078490.59735.6E.
    1. Yang W.-S., Jeng C.-Y., Wu T.-J., Tanaka S., Funahashi T., Matsuzawa Y., Wang J.-P., Chen C.-L., Tai T.-Y., Chuang L.-M. Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist, Rosiglitazone, Increases Plasma Levels of Adiponectin in Type 2 Diabetic Patients. Diabetes Care. 2002;25:376–380. doi: 10.2337/diacare.25.2.376.
    1. Tonelli J., Li W., Kishore P., Pajvani U.B., Kwon E., Weaver C., Scherer P.E., Hawkins M. Mechanisms of Early Insulin-Sensitizing Effects of Thiazolidinediones in Type 2 Diabetes. Diabetes. 2004;53:1621–1629. doi: 10.2337/diabetes.53.6.1621.
    1. Araki T., Emoto M., Konishi T., Ikuno Y., Lee E., Teramura M., Motoyama K., Yokoyama H., Mori K., Koyama H., et al. Glimepiride increases high-density lipoprotein cholesterol via increasing adiponectin levels in type 2 diabetes mellitus. Metabolism. 2009;58:143–148. doi: 10.1016/j.metabol.2008.09.006.
    1. Li G., Xie C., Lu S., Nichols R.G., Tian Y., Li L., Patel D., Ma Y., Brocker C.N., Yan T., et al. Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota. Cell Metab. 2017;26:672–685.e674. doi: 10.1016/j.cmet.2017.08.019.
    1. Sirico F., Bianco A., D’Alicandro G., Castaldo C., Montagnani S., Spera R., di Meglio F., Nurzynska D. Effects of Physical Exercise on Adiponectin, Leptin, and Inflammatory Markers in Childhood Obesity: Systematic Review and Meta-Analysis. Child. Obes. (Print) 2018;14:207–217. doi: 10.1089/chi.2017.0269.
    1. Becic T., Studenik C., Hoffmann G. Exercise Increases Adiponectin and Reduces Leptin Levels in Prediabetic and Diabetic Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Med. Sci. 2018;6:97. doi: 10.3390/medsci6040097.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren