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

Abstract

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.

Essential Amino Acid-Enriched Diet Alleviates Dexamethasone-Induced Loss of Muscle Mass and Function through Stimulation of Myofibrillar Protein Synthesis and Improves Glucose Metabolism in Mice

“…Furthermore, some EAAs have been demonstrated to stimulate glucose uptake in rodents [28][29][30] during OGTT. Therefore, EAA supplementation has been utilized as a potential nutritional treatment for various muscle atrophy conditions, including aging [31], obesity [32], and osteoporosis [33]. According to the above-mentioned results, it is suggested that EAAs may alleviate muscle atrophy induced by DEX via enhancement of muscle protein synthesis and glucose metabolism.…”

Dietary Amino Acid Source Elicits Sex‐Specific Metabolic Response to Diet‐Induced NAFLD in Mice

“…We postulated differential AA availability between dietary free AAs and casein that may impact metabolic homeostasis and associated hepatic gene expression in response to a WD. As NAFLD is a sexually dimorphic disease and hepatic AA homeostasis is also sexually dimorphic, [3,4,19] we studied both male and female mice.…”

Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice

“…As ERα is known to interact with liver LXR α and inhibit its function [ 69 ], a plausible mechanism for Enho regulation by estrogen involves ERα repression of LXRα-mediated inhibition of Enho transcription. In a recently available dataset, we found reduced hepatic Enho expression in OVX vs SHAM both in ERα f/f as well as in liver specific ERα knockout (LERKO) mice [ 70 ], suggesting additional non-ERα or extra hepatic regulation by estrogen. This is further supported by the reported increase in hepatic Enho expression following E2 treatment to LERKO mice [ 71 ].…”