GPER1 and metabolic disease: Hepatic GPER1 depletion largely reversed the protective roles of E2 on the OVX-induced body weight gain (Fig. 1C), WAT gain (Fig. 1D), glucose homeostasis impairment, and insulin resistance (Fig. 1, E–K), liver weight gain (Fig. 1L), hepatic and serum lipid metabolism disorders (Fig. 1, M–P), and hepatic inflammation (Fig. 1, Q and R) in female mice, which indicate that hepatic GPER1 involved in the protective effects of E2 on OVX-induced metabolic diseases.