Affordable Access

Aster-B-dependent estradiol synthesis protects female mice from diet-induced obesity

Authors
  • Xiao, Xu
  • Kennelly, John Paul
  • Feng, An-Chieh
  • Cheng, Lijing
  • Romartinez-Alonso, Beatriz
  • Bedard, Alexander H
  • Gao, Yajing
  • Cui, Liujuan
  • Young, Stephen G
  • Schwabe, John WR
  • Tontonoz, Peter
Publication Date
Feb 15, 2024
Source
eScholarship - University of California
Keywords
License
Unknown
External links

Abstract

Aster proteins mediate the nonvesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER). However, the importance of nonvesicular sterol movement for physiology and pathophysiology in various tissues is incompletely understood. Here we show that loss of Aster-B leads to diet-induced obesity in female but not in male mice, and that this sex difference is abolished by ovariectomy. We further demonstrate that Aster-B deficiency impairs nonvesicular cholesterol transport from the PM to the ER in ovaries in vivo, leading to hypogonadism and reduced estradiol synthesis. Female Aster-B-deficient mice exhibit reduced locomotor activity and energy expenditure, consistent with established effects of estrogens on systemic metabolism. Administration of exogenous estradiol ameliorates the diet-induced obesity phenotype of Aster-B-deficient female mice. These findings highlight the key role of Aster-B-dependent nonvesicular cholesterol transport in regulating estradiol production and protecting females from obesity.

Report this publication

Statistics

Seen <100 times