Adipolin/C1qdc2/CTRP12 Protein Functions As an Adipokine That Improves Glucose Metabolism

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Aug 19

PMID 21849507

Citations 71

Authors

Takashi Enomoto

Koji Ohashi

Rei Shibata

Akiko Higuchi

Sonomi Maruyama

Yasuhiro Izumiya

Kenneth Walsh

Toyoaki Murohara

Noriyuki Ouchi

Affiliations

Soon will be listed here.

Abstract

Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. Adipose tissue secretes various bioactive molecules, referred to as adipokines, whose dysregulation can mediate changes in glucose homeostasis and inflammatory responses. Here, we identify C1qdc2/CTRP12 as an insulin-sensitizing adipokine that is abundantly expressed by fat tissues and designate this adipokine as adipolin (adipose-derived insulin-sensitizing factor). Adipolin expression in adipose tissue and plasma was reduced in rodent models of obesity. Adipolin expression was also decreased in cultured 3T3-L1 adipocytes by treatment with inducers of endoplasmic reticulum stress and inflammation. Systemic administration of adipolin ameliorated glucose intolerance and insulin resistance in diet-induced obese mice. Adipolin administration also reduced macrophage accumulation and proinflammatory gene expression in the adipose tissue of obese mice. Conditioned medium from adipolin-expressing cells diminished the expression of proinflammatory cytokines in response to stimulation with LPS or TNFα in cultured macrophages. These data suggest that adipolin functions as an anti-inflammatory adipokine that exerts beneficial actions on glucose metabolism. Therefore, adipolin represents a new target molecule for the treatment of insulin resistance and diabetes.

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References

Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K . PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes. 2001; 50(9):2094-9. DOI: 10.2337/diabetes.50.9.2094. View

Wei Z, Peterson J, Wong G . Metabolic regulation by C1q/TNF-related protein-13 (CTRP13): activation OF AMP-activated protein kinase and suppression of fatty acid-induced JNK signaling. J Biol Chem. 2011; 286(18):15652-65. PMC: 3091174. DOI: 10.1074/jbc.M110.201087. View

Xu H, Barnes G, Yang Q, Tan G, Yang D, Chou C . Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003; 112(12):1821-30. PMC: 296998. DOI: 10.1172/JCI19451. View

Hug C, Wang J, Ahmad N, Bogan J, Tsao T, Lodish H . T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci U S A. 2004; 101(28):10308-13. PMC: 478568. DOI: 10.1073/pnas.0403382101. View

Pauli V, Juge-Aubry C, Boss O, PERNIN A, Chin W, Cusin I . Direct effects of leptin on brown and white adipose tissue. J Clin Invest. 1998; 100(11):2858-64. PMC: 508492. DOI: 10.1172/JCI119834. View

Wong G, Wang J, Hug C, Tsao T, Lodish H . A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci U S A. 2004; 101(28):10302-7. PMC: 478567. DOI: 10.1073/pnas.0403760101. View

Shibata R, Ouchi N, Kihara S, Sato K, Funahashi T, Walsh K . Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling. J Biol Chem. 2004; 279(27):28670-4. DOI: 10.1074/jbc.M402558200. View

Ouchi N, Parker J, Lugus J, Walsh K . Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011; 11(2):85-97. PMC: 3518031. DOI: 10.1038/nri2921. View

Zhang Y, Matheny M, Zolotukhin S, Tumer N, Scarpace P . 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. 2002; 1584(2-3):115-22. DOI: 10.1016/s1388-1981(02)00298-6. View

10.

Weisberg S, McCann D, Desai M, Rosenbaum M, Leibel R, Ferrante Jr A . Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003; 112(12):1796-808. PMC: 296995. DOI: 10.1172/JCI19246. View

11.

Spiegelman B, Flier J . Adipogenesis and obesity: rounding out the big picture. Cell. 1996; 87(3):377-89. DOI: 10.1016/s0092-8674(00)81359-8. View

12.

Combs T, Berg A, Rajala M, Klebanov S, Iyengar P, Jimenez-Chillaron J . Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes. 2003; 52(2):268-76. DOI: 10.2337/diabetes.52.2.268. View

13.

Izumiya Y, Hopkins T, Morris C, Sato K, Zeng L, Viereck J . Fast/Glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice. Cell Metab. 2008; 7(2):159-72. PMC: 2828690. DOI: 10.1016/j.cmet.2007.11.003. View

14.

Hotamisligil G . Inflammation and metabolic disorders. Nature. 2006; 444(7121):860-7. DOI: 10.1038/nature05485. View

15.

Ouchi N, Higuchi A, Ohashi K, Oshima Y, Gokce N, Shibata R . Sfrp5 is an anti-inflammatory adipokine that modulates metabolic dysfunction in obesity. Science. 2010; 329(5990):454-7. PMC: 3132938. DOI: 10.1126/science.1188280. View

16.

Shibata R, Sato K, Pimentel D, Takemura Y, Kihara S, Ohashi K . Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005; 11(10):1096-103. PMC: 2828682. DOI: 10.1038/nm1295. View

17.

Gregor M, Hotamisligil G . Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011; 29:415-45. DOI: 10.1146/annurev-immunol-031210-101322. View

18.

Schenk S, Saberi M, Olefsky J . Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest. 2008; 118(9):2992-3002. PMC: 2522344. DOI: 10.1172/JCI34260. View

19.

Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S . Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003; 423(6941):762-9. DOI: 10.1038/nature01705. View

20.

Ohashi K, Parker J, Ouchi N, Higuchi A, Vita J, Gokce N . Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem. 2009; 285(9):6153-60. PMC: 2825410. DOI: 10.1074/jbc.M109.088708. View