Dietary essential amino acids restore liver metabolism in ovariectomized mice via hepatic estrogen receptor α

Nat Commun. 2021 Nov 25;12(1):6883. doi: 10.1038/s41467-021-27272-x.


In female mammals, the cessation of ovarian functions is associated with significant metabolic alterations, weight gain, and increased susceptibility to a number of pathologies associated with ageing. The molecular mechanisms triggering these systemic events are unknown because most tissues are responsive to lowered circulating sex steroids. As it has been demonstrated that isoform alpha of the estrogen receptor (ERα) may be activated by both estrogens and amino acids, we test the metabolic effects of a diet enriched in specific amino acids in ovariectomized (OVX) mice. This diet is able to block the OVX-induced weight gain and fat deposition in the liver. The use of liver-specific ERα KO mice demonstrates that the hepatic ERα, through the control of liver lipid metabolism, has a key role in the systemic response to OVX. The study suggests that the liver ERα might be a valuable target for dietary treatments for the post-menopause.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Branched-Chain / pharmacology
  • Amino Acids, Branched-Chain / therapeutic use
  • Amino Acids, Essential / pharmacology*
  • Amino Acids, Essential / therapeutic use
  • Animals
  • Diet Therapy
  • Estrogen Receptor alpha / deficiency
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Lipid Metabolism / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Ovariectomy / adverse effects*
  • Sex Characteristics
  • Transcriptome / drug effects
  • Weight Gain / drug effects


  • Amino Acids, Branched-Chain
  • Amino Acids, Essential
  • Estrogen Receptor alpha