Estrogen Regulates Daily Metabolic Rhythms in Female Mice

Abstract

One‐third of women are obese. Moreover, after menopause, women are increasingly susceptible to obesity comorbidities such as metabolic syndrome and cardiovascular disease, suggesting that estrogen regulates these processes. Shift work, which disrupts circadian rhythms, also increases the risk of obesity and cardiovascular disease in women. In this study, we sought to examine the role of estrogen in regulating daily rhythms associated with the development of obesity. The circadian system controls daily, 24‐h rhythms of behavior and physiology such as the sleep‐wake cycle and the eating rhythm. Our lab previously found that high‐fat diet feeding in male mice, which caused diet‐induced obesity, also disrupted daily rhythms of eating behavior. Male mice typically had robust eating rhythms (eating consolidated during the night) on low‐fat diet (LFD). However, when placed on high‐fat diet (HFD), male mice ate arrhythmically throughout the day. Since previous studies demonstrated that female mice were resistant to diet‐induced obesity, we aimed to determine whether daily metabolic rhythms were also protected from the effects of high‐fat feeding in females. Female C57BL/6J mice (6 weeks old) were ovariectomized and implanted subcutaneously with either a physiological dose of 17β‐estradiol or vehicle (sesame oil) in silastic tubing. At 7 weeks old, females were single‐housed in cages in light‐tight boxes in 12L:12D and fed LFD (10% kcal fat) for 1 week and then HFD (45% kcal fat) for 1 week. Locomotor activity and eating behavior rhythms were continuously measured with infrared sensors and video cameras, respectively. Body weight, food intake, body composition and fasting blood glucose were also measured. Consistent with previous studies, we found that estrogen replacement in ovariectomized mice inhibited HFD‐induced weight gain and adiposity in females. In contrast to males, whose daily rhythm of eating behavior was abrogated during high‐fat feeding, intact females had robust eating behavior rhythms on high‐fat diet. However, after ovariectomy, females had low‐amplitude or arrhythmic eating behavior during high‐fat feeding. The robust daily rhythm of eating behavior was rescued in ovariectomized females with estrogen replacement. Our data show that estrogen confers robust, high‐amplitude eating behavior rhythms during high‐fat feeding in female mice. Notably, these females are also protected from diet‐induced obesity. Together, our data show that regulation of daily metabolic rhythms is markedly different in males and females.Support or Funding InformationThis study was funded by National Institutes of Health grants R03DK098321, P20GM103527, K01DK098321, and P30DK058404, and the University of Kentucky.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.