TY - JOUR
T1 - Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism
AU - Petersen, Pia Steen
AU - Jin, Chunyu
AU - Madsen, Andreas Nygaard
AU - Rasmussen, Maria
AU - Kuhre, Rune
AU - Egerod, Kristoffer L
AU - Nielsen, Lars Bo
AU - Schwartz, Thue W
AU - Holst, Birgitte
PY - 2011/11
Y1 - 2011/11
N2 - GPR39, a constitutively active 7TM receptor important for glucose-induced insulin secretion and maturation of pancreatic β-cell function, is upregulated 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.
AB - GPR39, a constitutively active 7TM receptor important for glucose-induced insulin secretion and maturation of pancreatic β-cell function, is upregulated 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.
U2 - 10.1096/fj.11-184531
DO - 10.1096/fj.11-184531
M3 - Journal article
C2 - 21784784
SN - 0892-6638
SP - 3803
EP - 3814
JO - F A S E B Journal
JF - F A S E B Journal
M1 - 4
ER -
