Exploration of Medicine

Table 2. 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
ERα	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	Abundant in hepatocytes and inactivated HSCs
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	----	----

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ER: estrogen receptor; GPR30: G protein-coupled receptor 30; ↑ increased; ↓ decreased; ---- sex-balanced studies not available

Declarations

Author contributions

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.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

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.

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