Estrogen receptors and its role in sexual dimorphism of NAFLD
|ERα||ERα-knockout mice||Higher visceral fat accumulation and reduced energy expenditure||ERα-knockout mice||Impaired glucose tolerance, hyperglycemia, hyperinsulinemia||Abundant in hepatocytes and inactivated HSCs|
|E2 treatment in ovariectomized mice||Promotes fatty acid oxidation; improves insulin sensitivity; reduce lipid synthesis; improves glucose homeostasis||E2 treatment||Protected against HFD-induced insulin resistance and adipose tissue inflammation|
|ERβ||ERβ-knockout mice||Increased body weight gain and fat deposition under HFD-treatment||----||----||Less expression in hepatocytes, high expression in fibrotic livers and activated HSCs|
|----||----||ERβ-selective agonists (β-LGND2 and WAY200070)||Inhibits body weight and white adipose tissue, and increases metabolism in male HFD mice; improves plasma insulin levels and glucose tolerance|
|ERβ-knockout mice||Protected against diet-induced IR and glucose intolerance||ERβ-knockout mice||No hepatic steatosis and decreased in serum cholesterol levels|
|GPER or GPR 30||GPER-knockout mice||↓ Levels of HDL; ↑ in fat liver accumulation||GPER-knockout mice||↑ Levels of HDL; ↓ in fat liver accumulation;||Expressed in hepatocytes and quiescent HSCs|
|GPER-knockout mice||Moderate obesity and larger adipocyte size beginning later age||GPER-knockout mice||Moderate obesity and larger adipocyte size beginning earlier age|
|GPER-knockout mice||Protected from HFD-induced obesity, blood glucose intolerance, and insulin resistance||----||----|
ER: estrogen receptor; GPR30: G protein-coupled receptor 30; ↑ increased; ↓ decreased; ---- sex-balanced studies not available
NCS; PJG; CT and NR contributed conception and design of the review and in the writing of the different sections of the review. All authors contributed to manuscript revision, read and approved the submitted version.
The authors declare that they have no conflicts of interest.
NCS is funded by the Department of Science and Technology-Philippine Council for Health Research and Development (DOST-PCHRD), Philippines; PJG is supported by Post-doctoral Fellowships 2020 from Fondazione Umberto Veronesi, Italy; NR is funded by Fondazione Cassa di Risparmio di Trieste (CRTrieste) and by Fondazione Italiana Fegato ONLUS.
© The Author(s) 2020.