| First Author | Meda C | Year | 2020 |
| Journal | Mol Metab | Volume | 32 |
| Pages | 97-108 | PubMed ID | 32029233 |
| Mgi Jnum | J:305810 | Mgi Id | MGI:6705613 |
| Doi | 10.1016/j.molmet.2019.12.009 | Citation | Meda C, et al. (2020) Hepatic ERalpha accounts for sex differences in the ability to cope with an excess of dietary lipids. Mol Metab 32:97-108 |
| abstractText | OBJECTIVE: Among obesity-associated metabolic diseases, non-alcoholic fatty liver disease (NAFLD) represents an increasing public health issue due to its emerging association with atherogenic dyslipidemia and cardiovascular diseases (CVDs). The lower prevalence of NAFLD in pre-menopausal women compared with men or post-menopausal women led us to hypothesize that the female-inherent ability to counteract this pathology might strongly rely on estrogen signaling. In female mammals, estrogen receptor alpha (ERalpha) is highly expressed in the liver, where it acts as a sensor of the nutritional status and adapts the metabolism to the reproductive needs. As in the male liver this receptor is little expressed, we here hypothesize that hepatic ERalpha might account for sex differences in the ability of males and females to cope with an excess of dietary lipids and counteract the accumulation of lipids in the liver. METHODS: Through liver metabolomics and transcriptomics we analyzed the relevance of hepatic ERalpha in the metabolic response of males and females to a diet highly enriched in fats (HFD) as a model of diet-induced obesity. RESULTS: The study shows that the hepatic ERalpha strongly contributes to the sex-specific response to an HFD and its action accounts for opposite consequences for hepatic health in males and females. CONCLUSION: This study identified hepatic ERalpha as a novel target for the design of sex-specific therapies against fatty liver and its cardio-metabolic consequences. |
