The circadian system is a critical regulator of metabolism and obesity in males, but its role in regulating obesity in females is poorly understood. Because there are sex differences in the development of obesity and susceptibility to obesity-related disorders, we sought to determine the role of estrogens in regulating the circadian mechanisms underlying diet-induced obesity. When fed high-fat diet, C57BL/6J male mice gain weight, whereas females are resistant to diet-induced obesity. Here, we demonstrate that estradiol regulates circadian rhythms in females to confer resistance to diet-induced obesity. We found that ovariectomized females with undetectable circulating estrogens became obese and had disrupted daily rhythms of eating behavior and locomotor activity when fed a high-fat diet. The phase of the liver molecular circadian rhythm was also altered by high-fat diet feeding in ovariectomized mice. Estradiol replacement in ovariectomized females a fed high-fat diet rescued these behavioral and tissue rhythms. Additionally, restoring the daily rhythm of eating behavior in ovariectomized females with time-restricted feeding inhibited diet-induced obesity and insulin resistance. Together, these data suggest that the circadian system is a target for treating obesity and its comorbidities in women after menopause, when circulating levels of estrogens are too low to protect their circadian rhythms.
|Journal||American Journal of Physiology - Endocrinology and Metabolism|
|State||Published - Dec 2019|
Bibliographical noteFunding Information:
This research was funded by National Institutes of Health (NIH) Grants R03-DK-107851, K01-DK-098321, P30-GM-127211, P30-DK-020579, P30-DK-058404, and UL1-TR-001998 as well as the Gertrude F. Ribble Grant and the University of Kentucky. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
© 2019 American Physiological Society. All rights reserved.
- Time-restricted feeding
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology (medical)