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- Title
Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance.
- Authors
Meilian Liu; Ruihua Xiang; Wilk, Sarah Ann; Ning Zhang; Sloane, Lauren B.; Azarnoush, Kian; Lijun Zhou; Hongzhi Chen; Guangda Xiang; Walter, Christi A.; Austad, Steven N.; Musi, Nicolas; DeFronzo, Ralph A.; Asmis, Reto; Scherer, Philipp E.; Dong, Lily Q.; Feng Liu
- Abstract
The antidiabetic and antiatherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high serum levels of this adipokine. On the other hand, a significant correlation between adiponectin multimerization and its insulin-sensitizing effects has been demonstrated, suggesting a promising alternative therapeutic strategy. Here we show that transgenic mice overexpressing disulfide bond A oxidoreductaselike protein in fat (fDsbA-L) exhibited increased levels of total and the high-molecular-weight form of adiponectin compared with wild-type (WT) littermates. The fDsbA-L mice also displayed resistance to diet-induced obesity, insulin resistance, and hepatic steatosis compared with WT control mice. The protective effects of DsbA-L overexpression on diet-induced insulin resistance, but not increased body weight and fat cell size, were significantly decreased in adiponectin-deficient fDsbA-L mice (fDsbA-L/Ad-/-). In addition, the fDsbA-L/Ad-/- mice displayed greater activity and energy expenditure compared with adiponectin knockout mice under a high-fat diet. Taken together, our results demonstrate that DsbA-L protects mice from diet-induced obesity and insulin resistance through adiponectin-dependent and independent mechanisms. In addition, upregulation of DsbA-L could be an effective therapeutic approach for the treatment of obesity and its associated metabolic disorders.
- Subjects
HYPOGLYCEMIC agents; CARDIOVASCULAR diseases; ADIPOKINES; INSULIN resistance; SERUM; OBESITY treatment; ADIPONECTIN
- Publication
Diabetes, 2012, Vol 61, Issue 11, p2776
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db12-0169