Estradiol signaling mediates gender difference in visceral adiposity via autophagy

Cell Death & Disease
Zhipeng TaoZhiyong Cheng

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) aris...Continue Reading

References

Dec 1, 1991·Metabolism: Clinical and Experimental·J HaarboC Christiansen
Dec 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·D B LubahnO Smithies
May 1, 1996·American Journal of Epidemiology·D Goodman-Gruen, E Barrett-Connor
Feb 1, 1997·The Journal of Clinical Endocrinology and Metabolism·M GambaccianiA R Genazzani
Jan 1, 1997·Clinical Science·J B Prins, S O'Rahilly
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·P A HeineP S Cooke
Jan 11, 2001·Journal of Medicinal Chemistry·S R StaufferJ A Katzenellenbogen
Jun 19, 2001·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·M C NguyenJ G Kral
Jun 8, 2004·The Journal of Clinical Endocrinology and Metabolism·Erin E Kershaw, Jeffrey S Flier
May 19, 2005·The Journal of Biological Chemistry·Gary G Chiang, Robert T Abraham
Mar 29, 2006·Diabetes·Deborah J CleggStephen C Benoit
Apr 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stephane GestaC Ronald Kahn
Feb 7, 2007·The Journal of Biological Chemistry·Nina HeldringAshley C W Pike
Jul 27, 2007·American Journal of Physiology. Endocrinology and Metabolism·Haifei ShiRandy J Seeley
Jan 17, 2008·Obesity·Ellen W DemerathBradford Towne
May 6, 2008·Nature·Kirsty L SpaldingPeter Arner
Nov 14, 2008·The New England Journal of Medicine·T PischonE Riboli
Feb 18, 2009·The Journal of Clinical Investigation·Anurag Kumar SinghUrsula Seidler
Sep 3, 2009·Molecular and Cellular Endocrinology·Sandra GalicGregory R Steinberg
Oct 20, 2009·Nature Medicine·Zhiyong ChengMorris F White
Nov 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yong ZhangShengkan Jin
Jan 13, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·K N ManolopoulosK N Frayn
Feb 11, 2010·Cell·Noboru MizushimaBeth Levine
Oct 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yourka D TchoukalovaMichael D Jensen
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Feb 5, 2011·Acta Pharmacologica Sinica·Sunhyo Jeong, Michung Yoon
Mar 3, 2011·Journal of Cellular and Molecular Medicine·Pasquale ListaWalter Malorni
Mar 17, 2011·PloS One·Alessandra RigamontiChad A Cowan
Sep 13, 2011·Cell Metabolism·Rodrigo P A Barros, Jan-Åke Gustafsson
Jan 26, 2012·Diabetes·Eijiro Yamada, Rajat Singh
Jun 2, 2012·Biology of Sex Differences·Kalypso KarastergiouSusan K Fried
Aug 21, 2012·Breast Cancer Research and Treatment·Patricia M SheeanMelinda Stolley
Oct 12, 2012·Molecular Endocrinology·Deborah J Clegg
May 21, 2013·Biochimica Et Biophysica Acta·Ursula A White, Yourka D Tchoukalova
Jun 27, 2013·American Journal of Physiology. Endocrinology and Metabolism·Chongben ZhangZhen Yan

❮ Previous
Next ❯

Citations

Jul 5, 2018·Expert Opinion on Drug Metabolism & Toxicology·Cene SkubicDamjana Rozman
Aug 12, 2018·Journal of Lipid Research·Aaron P FrankDeborah J Clegg
Feb 28, 2020·International Journal of Molecular Sciences·Massimo De MartinisLia Ginaldi
Oct 18, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Claes OhlssonMarie K Lagerquist
Aug 25, 2019·Trends in Endocrinology and Metabolism : TEM·Zhiyong Cheng
Mar 17, 2021·Cell Death Discovery·Zhipeng TaoZhiyong Cheng
Jun 26, 2021·Journal of Veterinary Science·Jong Yeon KimHae Jeung Lee

❮ Previous
Next ❯

Methods Mentioned

BETA
lipidation
GTPase
protein assay

Related Concepts

Related Feeds

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagy & Metabolism

Autophagy preserves the health of cells and tissues by replacing outdated and damaged cellular components with fresh ones. In starvation, it provides an internal source of nutrients for energy generation and, thus, survival. A powerful promoter of metabolic homeostasis at both the cellular and whole-animal level, autophagy prevents degenerative diseases. It does have a downside, however--cancer cells exploit it to survive in nutrient-poor tumors.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

© 2022 Meta ULC. All rights reserved