G-protein-coupled receptor GPR10 is expressed in brain areas regulating energy metabolism. In this study, the effects of GPR10 gene deficiency on energy homeostasis in mice of both sexes fed either standard chow or a high-fat diet (HFD) were studied, with a focus on neuronal activation of PrRP neurons, and adipose tissue and liver metabolism. GPR10 deficiency in males upregulated the phasic and tonic activity of PrRP neurons in the nucleus of the solitary tract. GPR10 knockout (KO) males on a standard diet displayed a higher body weight than their wild-type (WT) littermates due to an increase in adipose tissue mass; however, HFD feeding did not cause weight differences between genotypes. Expression of lipogenesis genes was suppressed in the subcutaneous adipose tissue of GPR10 KO males. In contrast, GPR10 KO females did not differ in body weight from their WT controls, but showed elevated expression of lipid metabolism genes in the liver and subcutaneous adipose tissue compared to WT controls. An attenuated non-esterified fatty acids change after glucose load compared to WT controls suggested a defect in insulin-mediated suppression of lipolysis in GPR10 KO females. Indirect calorimetry did not reveal any differences in energy expenditure among groups. In conclusion, deletion of GPR10 gene resulted in changes in lipid metabolism in mice of both sexes, however in different extent. An increase in adipose tissue mass observed in only GPR10 KO males may have been prevented in GPR10 KO females owing to a compensatory increase in the expression of metabolic genes.

Institute of Molecular Genetics of the Czech Academy of Sciences 14220 Prague Czech Republic

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences 16610 Prague Czech Republic

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences 16610 Prague Czech Republic; Biomedical Research Center SAS of the Slovak Academy of Sciences 845 05 Bratislava Slovak Republic; Institute of Physiology Faculty of Medicine Comenius University in Bratislava 813 72 Bratislava Slovak Republic

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences 16610 Prague Czech Republic; Institute of Physiology of the Czech Academy of Sciences 14200 Prague Czech Republic

Institute of Physiology of the Czech Academy of Sciences 14200 Prague Czech Republic

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