In this study, mice carrying a disrupted gene encoding GPR 10 (GPR 10 KO) were studied to elucidate the function and importance of this receptor regarding metabolism. Female and male GPR 10 KO mice had higher body weight after I I and 15 weeks of age, respectively. The increased body weight was a result of increased fat mass. The obesity was much more pronounced in female mice, which also had a significant decrease in energy expenditure. In correlation to obesity, higher plasma levels of leptin, total cholesterol, and fractions of LDL and HDL were found in GPR10 KO compared to WT mice. Interestingly, GPR10 KO female mice had decreased relative food intake in correlation to higher hypothalamic expression levels of the anorexic signals CRH and POMC. In conclusion, female mice deficient of the gene encoding GPR10 develop higher body weight and obesity due to lower energy expenditure. (C) 2007 Elsevier Inc. All rights reserved.