Ovariectomy (OVX) leads to hyperphagia and weight gain in rats, which can be prevented by estradiol (E2) replacement; however, the role of endogenous E2 on feeding and energy homeostasis in female mice has not been well characterized. The primary goal of this study was to assess the relative contribution of increased energy intake and decreased energy expenditure to OVX-induced weight gain in female rats and mice. OVX led to hyperphagia in rats, but did not produce daily, nor cumulative, hyperphagia in mice. OVX decreased mass-specific metabolic rate in mice, but not in rats. OVX decreased home cage locomotor activity in both species. Pair-feeding attenuated OVX-induced weight gain in rats and produced both short- and long-term changes in expression of key hypothalamic genes involved in food intake and energy homeostasis, i.e., the anorexigenic neuropeptide pro-opiomelanocortin (POMC) and the orexigenic neuropeptides: melanin-concentrating hormone (MCH) and agouti-related peptide (AgRP). No differences in hypothalamic gene expression were observed between OVX’d and sham mice. The results suggest that OVX-induced weight gain is mediated by hyperphagia and reduced locomotor activity in rats, but that in mice, it is primarily mediated by reduced locomotor activity and metabolic rate.

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Ovariectomy (OVX) causes hyperphagia and weight gain in rats. Estradiol (E2) abolishes these effects. Some report that pair‐feeding (PF) of OVX rats does not prevent obesity, but this finding is not universal. The purpose of this study was to determine the contribution of energy intake to OVX‐induced obesity. Long‐Evans rats (16 wk old) were fed chow and housed at 23°C. Rats were either intra‐abdominally bilaterally OVX (n = 20) or they underwent sham surgery (n = 12). For 3 wk, OVX rats were either PF (n = 8) or given ad libitum (AL) access to chow (n = 12). OVX‐AL rats were hyperphagic and had tonically decreased dark‐phase activity (pre‐OVX = 116 +/− 2 m, post‐OVX = 80 +/− 3 m). PF attenuated, but did not prevent, OVX‐induced obesity (3 wk weight gain: SHAM = 10.2 +/− 8.5, PF = 28.5 +/− 8.5, OVX = 51 +/− 10.5 g), indicating a role for E2 in regulation of energy expenditure. Next we investigated potential neural mechanisms underlying E2‐modulation of energy homeostasis. Quantitative RT‐PCR was used to measure mRNA levels of various hypothalamic genes of interest of these rats. Compared to shams, OVX led to increased MCH mRNA, an effect that was normalized by PF. Additional research is needed to understand E2‐specific mechanisms regulating energy expenditure. Support: NIH HL‐56732.