Estradiol signaling mediates gender difference in visceral adiposity via autophagy article

Zhipeng Tao, Louise D. Zheng, Cayleen Smith, Jing Luo, Alex Robinson, Fabio A. Almeida, Zongwei Wang, Aria F. Olumi, Dongmin Liu, Zhiyong Cheng

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Article number309
JournalCell Death and Disease
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2018

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Estradiol signaling mediates gender difference in visceral adiposity via autophagy article'. Together they form a unique fingerprint.

  • Cite this

    Tao, Z., Zheng, L. D., Smith, C., Luo, J., Robinson, A., Almeida, F. A., Wang, Z., Olumi, A. F., Liu, D., & Cheng, Z. (2018). Estradiol signaling mediates gender difference in visceral adiposity via autophagy article. Cell Death and Disease, 9(3), [309]. https://doi.org/10.1038/s41419-018-0372-9