| Texto completo | |
| Autor(es): Mostrar menos - |
Alves, Ester S.
;
Santos, Jessica D. M.
;
Cruz, Alessandra G.
;
Camargo, Felipe N.
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Talarico, Carlos H. Z.
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Santos, Anne R. M.
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Silva, Carlos A. A.
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Morgan, Henrique J. N.
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Matos, Sandro L.
;
Araujo, Layanne C. C.
;
Camporez, Joao Paulo
Número total de Autores: 11
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| Tipo de documento: | Artigo Científico |
| Fonte: | PATHOPHYSIOLOGY; v. 32, n. 1, p. 14-pg., 2025-01-03. |
| Resumo | |
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with cardiometabolic risk. Although studies have shown that estradiol positively contributes to energy metabolism via estrogen receptor alpha (ER alpha), its role specifically in the liver is not defined. Therefore, this study aimed to evaluate the effects of ER alpha overexpression, specifically in the liver in mice fed a high-fat diet (HFD). Methods: Male C57BL/6J mice were divided into four groups, vehicle fed with regular chow (RC) (RC-Vehicle); vehicle fed an HFD (HFD-Vehicle); AAV-treated fed with RC (RC-AAV); and AAV-treated fed an HFD (HFD-AAV), for 6 weeks (8-10 mice per group). AAV was administered intravenously to induce ER alpha overexpression. Results: We demonstrate that overexpression of ER alpha in RC-fed mice reduces body fat (28%). These mice show increased oxygen consumption in cultured primary hepatocytes, both in basal (19%) and maximal respiration (34%). In HFD-fed mice, we showed a decrease in hepatic TAG content (43%) associated with improved hepatic insulin sensitivity (145%). Conclusions: From this perspective, our results prove that hepatic ER alpha signaling is responsible for some of the metabolic protective effects of estrogen in mice. Overexpression of ER alpha improves hepatocyte mitochondrial function, consequently reducing hepatic lipid accumulation and protecting animals from hepatic steatosis and hepatic insulin resistance. Further investigations will be needed to determine the exact molecular mechanism by which ER alpha improves hepatic metabolic health. (AU) | |
| Processo FAPESP: | 18/04956-5 - Impacto do receptor de estrogênio alpha na Doença Hepática Gordurosa não Alcoólica e metabolismo energético do fígado |
| Beneficiário: | João Paulo Gabriel Camporez |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |