Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism

FASEB J. 2011 Nov;25(11):3803-14. doi: 10.1096/fj.11-184531. Epub 2011 Jul 22.


GPR39, a constitutively active 7TM receptor important for glucose-induced insulin secretion and maturation of pancreatic β-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Diet, High-Fat
  • Energy Metabolism
  • Female
  • Gene Expression Profiling
  • Lipid Metabolism / genetics
  • Male
  • Mice
  • Obesity / metabolism*
  • Oxygen Consumption
  • Receptors, G-Protein-Coupled / deficiency*


  • GPR39 protein, mouse
  • Receptors, G-Protein-Coupled