Relationship between blood glucose levels and hepatic Fto mRNA expression in mice

Common variants in the fat mass and obesity associated (FTO) gene are associated with obesity and type 2 diabetes. Fto-deficient mice develop hepatic insulin resistance, leading to the hypothesis that hepatic Fto plays a role in the regulation of glucose metabolism and that hepatic Fto expression is regulated by metabolic states. We found that hepatic Fto mRNA levels were increased by fasting in mice. Intraperitoneal glucose injection reduced hepatic Fto mRNA levels without significant changes in body weight in fasted mice. The inverse correlation between Fto mRNA and glucose remained significant after adjusting for body weight. There were positive correlations between hepatic Fto mRNA expression and gluconeogenic gene expression. These data support the hypothesis that hepatic Fto expression changes in response to metabolic states and glucose reduces hepatic Fto mRNA expression independently of body weight. Hepatic Fto may participate in the feedback regulation of glucose metabolism via gluconeogenesis.

Research highlights
► Intraperitoneal glucose injection reverses fasting-induced increase in hepatic Fto mRNA expression in mice.
► Hepatic Fto mRNA levels are inversely correlated with blood glucose levels independent of body weight in mice.
► Hepatic Fto mRNA levels are positively correlated with expression of gluconeogenic genes, Pepck and G6pase.