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Abstract
Male mice fed high-fat diet become obese, but female mice are resistant to diet-induced weight gain. We previously found that circulating estradiol in females protects their daily rhythms from disruption by high-fat feeding to prevent diet-induced obesity. The goal of this study was to determine the effects of estradiol on daily metabolic rhythms in male mice. Male C57BL/6J mice were treated with estradiol and fed high-fat diet for 2 weeks. We measured the effects of high-fat diet feeding on daily rhythms of eating behavior and locomotor activity, and on the phases, or timing, of circadian rhythms in central and peripheral tissues. We found that males treated with estradiol had lower blood glucose when fed high-fat diet than males treated with vehicle even though there were no effects of estradiol treatment on body weight and adiposity. There was no effect of estradiol on the daily rhythm of eating behavior as it was low-amplitude or arrhythmic during high-fat diet feeding in both vehicle- and estradiol-treated males. Locomotor activity rhythms were also unaffected by estradiol treatment. Likewise, the phases of circadian rhythms in the suprachiasmatic nucleus (SCN), liver, muscle, and other peripheral tissues were not altered by estradiol treatment. Thus, treatment of male mice with estradiol did not protect daily rhythms from disruption by high-fat diet, as it does in females. Together these data suggest that the mechanisms underlying sex differences in daily metabolic rhythms are complex and may require both developmental and adult exposure to hormones.
Document Type
Article
Publication Date
2026
Digital Object Identifier (DOI)
https://doi.org/10.1371/journal.pone.0343513
Funding Information
This study was funded by the National Institute of Health grants R01DK124774 (to JSP), P20GM103527 (Research Project Leader JSP), TL1TR001997 (to VMA), and P30GM127211, the Diabetes Research Center at Washington University in St. Louis P30DK020579 (pilot grant to JSP), the National Science Foundation grant IOS-2045267 (to JSP), The Gertrude F. Ribble Trust (to VMA and OBO), the University of Kentucky. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Repository Citation
Osborne, W. Brad; Vöcking, Oliver; Alvord, Victoria; Omotola, Oluwabukola; Katsumata, Yuriko; and Pendergast, Julie S., "Exogenous estradiol does not regulate daily metabolic rhythms underlying diet-induced obesity in male mice" (2026). Biology Faculty Publications. 234.
https://uknowledge.uky.edu/biology_facpub/234
Notes/Citation Information
© 2026 Osborne et al . This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.