Poster Topical Area: Obesity

Location: Hall D

Poster Board Number: 644

P23-017 - Estradiol signaling mediates gender difference in visceral adiposity via autophagy

Sunday, Jun 10
8:00 AM – 6:00 PM

Objectives: 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.

Methods: Here we studied the mechanism of gender difference of adiposity with C57BL/6J and estrogen receptor a (ERa) knockout mice, with a focus on estradiol signaling and autophagy in adipocytes.

Results: We found that the gender difference in visceral fat distribution was 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 ERa and more active autophagy in males vs. females. However, deletion of ERa normalized autophagy activity and abolished the gender difference in visceral adiposity. In line with the adiposity-reducing effect of the ERa-autophagy axis, we found that downregulation of ERa and increased autophagy activity were required for adipogenesis, while induction of estradiol signaling dampened autophagy and drastically prevented adipogenesis. Mechanistically, the estradiol-ERa signaling activated mTOR, which phosphorylated and inhibited ULK1, thereby suppressing autophagy and adipogenesis.

Conclusions: Our study suggests that the lower visceral adiposity in the females (vs. the males) arises from a more active estradiol-ERa signaling, which tunes down autophagy and adipogenesis.

Funding Source: USDA National Institute of Food and Agriculture Hatch Project 1007334 (ZC), NIH grant R18DK091811 (FAA), and NIH grant 1R01AT007077 (DL).

CoAuthors: Zhipeng Tao – Virginia Tech; Louise Zheng – Virginia Tech; Cayleen Smith – Virginia Tech; Jing Luo – Virginia Tech; Alex Robinson – Virginia Tech; Fabio Almeida – University of Nebraska Medical Center; Zongwei Wang – Harvard Medical School, Massachusetts General Hospital ; Aria Olumi – Harvard Medical School, Massachusetts General Hospital; Dongmin Liu – Virginia Tech

Zhiyong Cheng

Assistant Professor
Virginia Tech
Blacksburg, Virginia