Estrogen receptors and its role in sexual dimorphism of NAFLD

Receptor Female Effect(s) Male Effect(s) Notes
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