Sex Dimorphism in the Fgf21 Gene Expression in Liver and Adipose Tissues is Dependent on the Metabolic Condition

摘要

Fibroblast growth factor-21 (FGF21) beneficially affects carbohydrate and lipid metabolism. Previously, a sex-specific activation of Fgf21 expression was observed in humans and animals with metabolic diseases. It is unknown whether the sex differencesin the Fgfll expression are manifested in response to the natural physiological situations of fasting and refeeding. The aim of this work was to determine liver, White Adipose Tissue (WAT) and Brown Adipose Tissue (BAT) expression of genes related to FGF21 signaling in response to 24 h fasting, 6 h refeeding (after 24 h fasting) and Diet-Induced Obesity (DIO) in C57B1 mice of both sexes. Obesity was induced by the consumption of palatable food for 10 weeks. mRNA levels of peroxisome proliferator-activated receptor-a and -y (Ppara, Ppary), FGF21 (Fgfil), coactivator of FGF receptors (Klb) and transcriptional coactivator (Pgc-la) were measured by RT-PCR. The study showed that the fasting-induced increases in hepatic Fgfll gene expression and circulatingFGF21 levels, as well as refeeding-induced increases in local WAT and BAT Fgfll gene expression, were biased toward femajles^ DIO-induced increase in circulating FGF21 levels, as well as in Fgfll gene expression in the liver and BAT, were biased towardmales. Considering that FGF21 is a novel metabolic regulator of energy homeostasis, sex differences in the responses to anabolic and catabolic stimulus could have translational implications for novel therapeutic outcomes.