title: Adipolin/C1qdc2/CTRP12 protein functions as an adipokine that improves glucose metabolism.
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.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Enomoto
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.forename: Akiko
authors.initials: A
authors.lastname: Higuchi
authors.forename: Sonomi
authors.initials: S
authors.lastname: Maruyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Izumiya
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
mesh_terms: D041721:3T3-L1 Cells; D054392:Adipokines / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009765:Obesity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054392:Adipokines; C568466:C1qtnf12 protein, mouse; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose