Estradiol signaling mediates gender difference in visceral adiposity via autophagy

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dc.contributor.authorTao, Zhipengen
dc.contributor.authorZheng, Louise D.en
dc.contributor.authorSmith, Cayleenen
dc.contributor.authorLuo, Jingen
dc.contributor.authorRobinson, Alexen
dc.contributor.authorAlmeida, Fabio A.en
dc.contributor.authorWang, Zongweien
dc.contributor.authorOlumi, Aria F.en
dc.contributor.authorLiu, Dongminen
dc.contributor.authorCheng, Zhiyongen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessioned2018-07-24T17:01:39Zen
dc.date.available2018-07-24T17:01:39Zen
dc.date.issued2018en
dc.description.abstractExcessive adiposity (particularly visceral fat mass) increases the risks of developing metabolic syndrome. Women have lower deposit of visceral fat than men, and this pattern becomes diminished postmenopausally, but the underlying mechanism remains largely unknown. Here, we show that the gender difference in visceral fat distribution is controlled by an estradiol–autophagy axis. In C57BL/6J and wild-type control mice, a higher visceral fat mass was detected in the males than in the females, which was associated with lower expression of estrogen receptor α (ERα) and more active autophagy in males vs. females. However, deletion of ERα normalized autophagy activity and abolished the gender difference in visceral adiposity. In line with the adiposity-reducing effect of the ERα–autophagy axis, we found that downregulation of ERα and increased autophagy activity were required for adipogenesis, while induction of estradiol signaling dampened autophagy and drastically prevented adipogenesis. Mechanistically, the estradiol-ERα signaling activated mTOR, which phosphorylated and inhibited ULK1, thereby suppressing autophagy and adipogenesis. Together, our study suggests that the lower visceral adiposity in the females (vs. the males) arises from a more active estradiol-ERα signaling, which tunes down autophagy and adipogenesis.en
dc.description.sponsorshipUSDAen
dc.description.sponsorshipUSDA: National Institute of Food and Agriculture Hatch Project 1007334en
dc.description.sponsorshipNational Institutes of Healthen
dc.description.sponsorshipNIH: R18DK091811en
dc.description.sponsorshipNIH: 1R01AT007077en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41419-018-0372-9en
dc.identifier.issue3en
dc.identifier.urihttp://hdl.handle.net/10919/84333en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleEstradiol signaling mediates gender difference in visceral adiposity via autophagyen
dc.title.serialCell Death & Diseaseen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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