| First Author | Petersen PS | Year | 2011 |
| Journal | FASEB J | Volume | 25 |
| Issue | 11 | Pages | 3803-14 |
| PubMed ID | 21784784 | Mgi Jnum | J:178419 |
| Mgi Id | MGI:5298318 | Doi | 10.1096/fj.11-184531 |
| Citation | Petersen PS, et al. (2011) Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism. FASEB J 25(11):3803-14 |
| abstractText | GPR39, a constitutively active 7TM receptor important for glucose-induced insulin secretion and maturation of pancreatic beta-cell function, is up-regulated in adipose tissue on abstinence from food and chemically induced diabetes. In the present study, we investigated the effect of GPR39 deficiency on body weight and adipocyte metabolism. GPR39-deficient mice were subjected to a high-fat diet and body composition, glucose tolerance, insulin secretion, food intake, and energy expenditure were evaluated. The cell biology of adipocyte metabolism was studied on both mRNA and protein levels. A significant increase in body weight corresponding to a 2-fold selective increase in fat mass was observed in GPR39-deficient mice fed a high-fat diet as compared with wild-type littermate controls fed the same diet. The GPR39-deficient animals had similar food intake but displayed almost eliminated diet-induced thermogenesis, measured by the oxygen consumption rate (Vo(2)) on change from normal to high-fat diet. Analysis of the adipose tissue for lipolytic enzymes demonstrated decreased level of phosphorylated hormone-sensitive lipase (HSL) and a decreased level of adipose triglyceride lipase (ATGL) by 35 and 60%, respectively, after food withdrawal in the GPR39-deficient mice. Extracellular signal-regulated kinases (ERK1/2), a signaling pathway known to be important for lipolysis, was decreased by 56% in the GPR39-deficient mice. GPR39 deficiency is associated with increased fat accumulation on a high-fat diet, conceivably due to decreased energy expenditure and adipocyte lipolytic activity. |
