title: Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism.
abstract: 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.
authors.affiliation: Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Pia Steen
authors.initials: PS
authors.lastname: Petersen
authors.forename: Chunyu
authors.initials: C
authors.lastname: Jin
authors.forename: Andreas Nygaard
authors.initials: AN
authors.lastname: Madsen
authors.forename: Maria
authors.initials: M
authors.lastname: Rasmussen
authors.forename: Rune
authors.initials: R
authors.lastname: Kuhre
authors.forename: Kristoffer L
authors.initials: KL
authors.lastname: Egerod
authors.forename: Lars Bo
authors.initials: LB
authors.lastname: Nielsen
authors.forename: Thue W
authors.initials: TW
authors.lastname: Schwartz
authors.forename: Birgitte
authors.initials: B
authors.lastname: Holst
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D004734:Energy Metabolism; D005260:Female; D020869:Gene Expression Profiling; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D009765:Obesity / Q000378:metabolism*; D010101:Oxygen Consumption; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency*
chemical_list: C512928:GPR39 protein, mouse; D043562:Receptors, G-Protein-Coupled