Poster Topical Area: Obesity
Location: Hall D
Poster Board Number: 644
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.