Format

Send to

Choose Destination
Cell Death Dis. 2018 Feb 22;9(3):309. doi: 10.1038/s41419-018-0372-9.

Estradiol signaling mediates gender difference in visceral adiposity via autophagy.

Author information

1
Department of Human Nutrition, Foods, and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, 24061, USA.
2
Department of Health Promotion, Social & Behavioral Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA.
3
Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
4
Department of Human Nutrition, Foods, and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, 24061, USA. doliu@vt.edu.
5
Department of Human Nutrition, Foods, and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, 24061, USA. zcheng@vt.edu.

Abstract

Excessive 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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center