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

Area of Science:

• Endocrinology
• Metabolic Science
• Nutritional Science

Background:

• Cessation of ovarian function in female mammals leads to metabolic changes, weight gain, and increased disease risk.
• The molecular basis for these systemic changes, driven by reduced sex steroids, remains unclear.
• Estrogen receptor alpha (ERα) can be activated by both estrogens and amino acids.

Purpose of the Study:

• To investigate the metabolic effects of an amino acid-enriched diet in ovariectomized (OVX) mice.
• To determine the role of hepatic ERα in mediating the systemic response to OVX.

Main Methods:

• Administration of a specific amino acid-enriched diet to OVX mice.
• Utilizing liver-specific ERα knockout (KO) mice to assess ERα function in hepatocytes.
• Monitoring body weight, fat deposition, and liver lipid metabolism.

Main Results:

• The amino acid-enriched diet effectively prevented OVX-induced weight gain and liver fat accumulation.
• Liver-specific ERα KO mice showed that hepatic ERα is crucial for regulating liver lipid metabolism.
• Hepatic ERα plays a key role in the systemic metabolic adaptations following OVX.

Conclusions:

• Dietary amino acid supplementation can mitigate menopause-associated metabolic disturbances.
• Hepatic ERα is a critical mediator of the metabolic consequences of ovarian function cessation.
• Liver ERα represents a potential therapeutic target for dietary interventions in post-menopausal women.