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Estradiol regulates daily rhythms underlying diet-induced obesity in female mice.

Authors
  • Omotola, Oluwabukola1
  • Legan, Sandra2
  • Slade, Emily3
  • Adekunle, Ayooluwatomiwa4
  • Pendergast, Julie S1
  • 1 Department of Biology, University of Kentucky, Lexington, Kentucky.
  • 2 Department of Physiology, University of Kentucky, Lexington, Kentucky.
  • 3 Department of Biostatistics, University of Kentucky, Lexington, Kentucky.
  • 4 Department of Epidemiology, University of Kentucky, Lexington, Kentucky.
Type
Published Article
Journal
AJP Endocrinology and Metabolism
Publisher
American Physiological Society
Publication Date
Dec 01, 2019
Volume
317
Issue
6
Identifiers
DOI: 10.1152/ajpendo.00365.2019
PMID: 31689145
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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.

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