Estrogens prevent metabolic dysfunctions induced by circadian disruptions in female mice

Authors: ZHU, LIANGRU - Children'S Nutrition Research Center (CNRC); ZOU, FANG - Children'S Nutrition Research Center (CNRC); YANG, YONGJIE - Children'S Nutrition Research Center (CNRC); XU, PINGWEN - Children'S Nutrition Research Center (CNRC); SAITO, KENJI - Children'S Nutrition Research Center (CNRC); HINTON, ANTENTOR - Children'S Nutrition Research Center (CNRC); YAN, XIAOFENG - Children'S Nutrition Research Center (CNRC); DING, HONGFANG - Children'S Nutrition Research Center (CNRC); WU, QI - Children'S Nutrition Research Center (CNRC); FUKUDA, MAKOTO - Children'S Nutrition Research Center (CNRC); SUN, ZHENG - Children'S Nutrition Research Center (CNRC); TONG, QINGCHUN - University Of Texas Health Science Center; XU, YONG - Children'S Nutrition Research Center (CNRC)

Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/20/2015
Publication Date: 6/1/2015
Citation: Zhu, L., Zou, F., Yang, Y., Xu, P., Saito, K., Hinton, A.O., Yan, X., Ding, H., Wu, Q., Fukuda, M., Sun, Z., Tong, Q., Xu, Y. 2015. Estrogens prevent metabolic dysfunctions induced by circadian disruptions in female mice. Endocrinology. 156(6):2114-2123.

Interpretive Summary: Obesity is a serious global health problem and is significant in those that do shift work or suffer from jet lag due to circadian clock disruption. Here we showed that the female sex hormone, estrogen, can substantially reduce fat accumulation in female mice challenged with jet lag. These findings highlight that estrogen signals as a potential therapeutic target for treatment of obesity at least in women.

Technical Abstract: Circadian disruption has become a significant factor contributing to the epidemics of obesity and insulin resistance. However, interventions to treat metabolic dysfunctions induced by circadian disruptions are limited. The ovarian hormone, estrogen, produces important antiobesity and antidiabetic effects in female animals and has profound effects on daily behavioral rhythms. Here, we show that in female mice depleted with endogenous estrogens, a jet-lag paradigm induced visceral fat accumulation and systemic insulin resistance, which were associated with altered expression of multiple circadian genes in the visceral fat depot. Interestingly, all these jet-lag-induced deficits were completely rescued in female mice supplemented with exogenous estrogens. We further examined 24-hour oscillations of circadian genes in adipose tissues in female mice with estrogen depletion or replacement and showed that expression levels of the circadian gene, period circadian protein homolog 2, oscillate in visceral adipose tissue in an estrogen-dependent manner. Together, our results indicate that estrogens interact with the intrinsic circadian clock in adipose tissue and prevent abnormal lipid accumulation caused by circadian disruptions.