Skiba-Cassy S, Lansard M, Panserat S, Medale F. Rainbow trout genetically selected for greater muscle fat content display increased activation of liver TOR signaling and lipogenic gene expression. Am J Physiol Regul Integr Comp Physiol 297: R1421-R1429, 2009. First published August 26, 2009; doi: 10.1152/ajpregu.00312.2009.-Genetic selection is commonly used in farm animals to manage body fat content. In rainbow trout, divergent selection for low or high muscle fat content leads to differences in utilization of dietary energy sources between the fat muscle line (FL) and the lean muscle line (LL). To establish whether genetic selection on muscle fat content affects the hepatic insulin/nutrient signaling pathway, we analyzed this pathway and the expression of several metabolism-related target genes in the livers of the two divergent lines under fasting and then refeeding conditions. Whereas glycemia returned to basal level 24 h after refeeding in FL trout, it remained elevated in the LL trout. Target of rapamycin (TOR) protein was more abundant in the livers of FL trout than in LL trout, and refeeding activation of the hepatic TOR signaling pathway (TOR, S6K1, and S6) was therefore enhanced. Genes related to glycolysis (glucokinase and pyruvate kinase) and gluconeogenesis (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) were only slightly affected by refeeding and genetic selection. Refeeding stimulated expression of lipogenic genes and the sterol-responsive element binding protein (SREBP1), and expression of fatty acid synthase, glucose-6-phosphate dehydrogenase, and serine dehydratase was predominant in the livers of FL fish compared with LL fish. In agreement with recent findings linking TOR to lipogenesis control, we concluded that genetic selection for muscle fat content resulted in overactivation of the TOR signaling pathway-associated lipogenesis and probably also improved utilization of glucose.