Estrogen receptors and its role in sexual dimorphism of NAFLD

ERαERα-knockout miceHigher visceral fat accumulation and reduced energy expenditureERα-knockout miceImpaired glucose tolerance, hyperglycemia, hyperinsulinemiaAbundant in hepatocytes and inactivated HSCs
E2 treatment in ovariectomized micePromotes fatty acid oxidation; improves insulin sensitivity; reduce lipid synthesis; improves glucose homeostasisE2 treatmentProtected against HFD-induced insulin resistance and adipose tissue inflammation
ERβERβ-knockout miceIncreased 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 miceProtected against diet-induced IR and glucose intoleranceERβ-knockout miceNo hepatic steatosis and decreased in serum cholesterol levels
GPER or GPR 30GPER-knockout mice↓ Levels of HDL; ↑ in fat liver accumulationGPER-knockout mice↑ Levels of HDL; ↓ in fat liver accumulation;Expressed in hepatocytes and quiescent HSCs
GPER-knockout miceModerate obesity and larger adipocyte size beginning later ageGPER-knockout miceModerate obesity and larger adipocyte size beginning earlier age
GPER-knockout miceProtected 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