Abstract
Fasting is often used for obesity correction but the “refeeding syndrome” limits its efficiency, and molecular mechanisms underlying metabolic response to different food availability are under investigation. Sex was shown to affect hormonal and metabolic reactions to fasting/refeeding. The aim of this study was to evaluate hormonal and transcriptional responses to fasting and refeeding in male and female C57Bl/6J mice. Sex asymmetry was observed both at the hormonal and transcriptional levels. Fasting (24 h) induced increase in hepatic Fgf21 gene expression, which was associated with elevation of plasma FGF21 and adiponectin levels, and the upregulation of expression of hepatic (Pparα, Cpt1α) and muscle (Cpt1β, Ucp3) genes involved in fatty acid oxidation. These changes were more pronounced in females. Refeeding (6 h) evoked hyperinsulinemia and increased hepatic expression of gene related to lipogenesis (Fasn) only in males and hyperleptinemia and increase in Fgf21 gene expression in muscles and adipose tissues only in females. The results suggest that in mice, one of the molecular mechanisms underlying sex asymmetry in hepatic Pparα, Cpt1α, muscle Cpt1β, and Ucp3 expression during fasting is hepatic Fgf21 expression, and the reason for sex asymmetry in hepatic Fasn expression during refeeding is male-specific hyperinsulinemia.
Highlights
The prevalence of obesity is increasing worldwide
We found sex asymmetry both in the hormonal and transcriptional responses to states differed by nutrient availability
Refeeding-induced male-specific hyperinsulinemia was accompanied by elevation of mRNA level of Fasn that regulates the rate of lipogenesis in the liver
Summary
The prevalence of obesity is increasing worldwide. Food restriction is known to be one of the main approaches to correct obesity. Effective use of fasting is limited by the “refeeding syndrome”, which is expressed as increased food intake after hunger and rapid weight gain due to the increase of white adipose tissue (WAT) mass. Fundamental aspects of metabolic homeostasis are known to be regulated differently in males and females [1,2,3,4]. There is increasing evidence that sex hormones regulate the expression of genes and proteins involved in lipid and glucose turnover [5]. Thousands of genes show sexual dimorphism in the liver [6], adipose tissues [5,7], and muscle [5]
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