Female mice and rats exhibit species-specific metabolic and behavioral responses to ovariectomy

Abstract

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.

Fig. 1

Body weight (A), daily caloric intake (B), energy balance (C) and energy expenditure (D) during 3 baseline and 20 post-surgical days in ovariectomized (triangles) and sham (circles) mice. The vertical dashed line indicates the end of the baseline period and the day when surgery was performed. Data represent mean ± SEM, n = 10/per group; (*) indicates p < 0.05 for OVX vs. SHAM mice and for pre-OVX baseline vs. post-OVX data. Abbreviation: OVX, ovariectomized.

Fig. 2

Body weight (A), daily caloric intake (B), energy balance (C) and energy expenditure (D) during 3 baseline days and 22 post-surgical days in ovariectomized (triangles) and sham (circles) rats. The vertical dashed line indicates the end of the baseline period and the day when surgery was performed. Data represent mean ± SEM, n = 12/OVX, n = 8/SHAM; (*) indicates p < 0.05 for OVX vs. SHAM rats. Abbreviation: OVX, ovariectomized.

Fig. 3

Dark-phase oxygen consumption (VO₂), normalized to body weight, in mice (A) and rats (C). Dark-phase locomotor activity in mice (B) and rats (D). The vertical dashed line indicates the end of the baseline period and the day when surgery was performed. Data represent mean ± SEM; mice: n = 10/per group, rats: n = 8/per group; (*) indicates p < 0.05 for OVX vs. sham animals; (#) indicates p < 0.05 for pre-OVX baseline vs. post-OVX data. Abbreviation: OVX, ovariectomized. *Note: different scales are used for mouse vs. rat data.

Fig. 4

Parametrial, mesenteric, and retroperitoneal fat pad weights excised at the termination of the study of OVX (gray bars) and sham (white bars) mice (A1, B1, C1; n = 10/group) and rats (A2, B2, C2; n = 12/group). Data represent mean ± SEM; (*) indicates p < 0.05 in OVX vs. sham animals. Abbreviation: OVX, ovariectomized.

Fig. 5

Body weight (A) and food intake (B) of OVX-AL (n = 4; closed triangles), OVX-PF (n = 5; open triangles), and SHAM (n = 4; circles) rats in the long-term pair-feeding study. Food intake values are 4-day averages; sham values represent food intake data obtained on non-estrous days only. Data represent mean ± SEM; (*) indicates p < 0.05 compared to OVX-AL, (#) indicates p < 0.05 compared to SHAM. Abbreviations: OVX, ovariectomized; AL, ad libitum-fed; PF, pair-fed.

Fig. 6

Hypothalamic MCH (A; note: different scale), POMC (B), and AgRP (C) mRNA, as measured by quantitative RT-PCR and normalized to expression of the housekeeping gene, RP27. Data represent mean ± SEM; (*) indicates p < 0.05 compared to OVX-AL, (#) indicates p < 0.05 compared to SHAM. Abbreviations: OVX, ovariectomy; AL, ad libitum; PF, pair-fed; MCH, melanin-concentrating hormone; POMC, pro-opiomelanocortin; AgRP, agouti-related peptide.