Fig. 1. Chemogenetic activation of ERα^vlVMH neurons stimulates physical activity and BAT thermogenesis in females.

(See also figs. S1 and S2.) (A) Representative trace of ERα-ZsGreen (+) neurons in the vlVMH of female mice treated with vehicle (1% dimethyl sulfoxide in saline) or 17β-estradiol (E2, 100 nM, 1s puff). (B to E) Summary of firing frequency (B and C) and resting membrane potential (D and E) (n = 13 or 14). (F) Schematic of the experimental strategy. (G and H) Effects of CNO (3 mg/kg) intraperitoneal injection on physical activity (G) and core temperature (H) in female mice with emitter intra-abdominally implanted (n = 4). (I and J) Effects of CNO injection on physical activity (I) and BAT temperature (J) in female mice with emitter implanted under BAT (n = 4). (K and L) Effects of chronic CNO treatment (twice/day, 3 mg/kg i.p. injection) on body weight gain (K) and energy intake (L) of ovariectomized (OVX) female mice (n = 3 or 4). (B to E) Data are presented for each cell. ***P < 0.001 in paired t tests. (G to L) Results are shown as means ± SEM. (G and H) *P < 0.05 in unpaired t tests. (I to L) *P < 0.05, **P < 0.01, and ****P < 0.0001 in two-way analysis of variance (ANOVA) analysis followed by post hoc Sidak tests.