Sex Differences in Liver, Adipose Tissue, and Muscle Transcriptional Response to Fasting and Refeeding in Mice

Cells. 2019 Nov 27;8(12):1529. doi: 10.3390/cells8121529.

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.

Keywords: adipose tissues; fasting refeeding; lipid glucose oxidation; liver; mice; muscle; sex-specific Fgf21 gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Animals
  • Carnitine O-Palmitoyltransferase / metabolism
  • Fasting / metabolism*
  • Fatty Acid Synthase, Type I / metabolism
  • Fatty Acids / metabolism
  • Female
  • Fibroblast Growth Factors / metabolism
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR alpha / metabolism
  • Quadriceps Muscle / metabolism*
  • Refeeding Syndrome / metabolism*
  • Sex Characteristics*
  • Uncoupling Protein 3 / metabolism

Substances

  • Fatty Acids
  • PPAR alpha
  • Ucp3 protein, mouse
  • Uncoupling Protein 3
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • CPT1B protein, mouse
  • Carnitine O-Palmitoyltransferase
  • Fasn protein, mouse
  • Fatty Acid Synthase, Type I