Metabolic benefits of inhibition of p38α in white adipose tissue in obesity

PLoS Biology
Shengjie ZhangHao Ying

Abstract

p38 has long been known as a central mediator of protein kinase A (PKA) signaling in brown adipocytes, which positively regulate the transcription of uncoupling protein 1 (UCP-1). However, the physiological role of p38 in adipose tissues, especially the white adipose tissue (WAT), is largely unknown. Here, we show that mice lacking p38α in adipose tissues display a lean phenotype, improved metabolism, and resistance to diet-induced obesity. Surprisingly, ablation of p38α causes minimal effects on brown adipose tissue (BAT) in adult mice, as evident from undetectable changes in UCP-1 expression, mitochondrial function, body temperature (BT), and energy expenditure. In contrast, genetic ablation of p38α in adipose tissues not only markedly facilitates the browning in WAT upon cold stress but also prevents diet-induced obesity. Consistently, pharmaceutical inhibition of p38α remarkably enhances the browning of WAT and has metabolic benefits. Furthermore, our data suggest that p38α deficiency promotes white-to-beige adipocyte reprogramming in a cell-autonomous manner. Mechanistically, inhibition of p38α stimulates the UCP-1 transcription through PKA and its downstream cAMP-response element binding protein (CREB), which form a posit...Continue Reading

References

Oct 29, 1998·Protein Expression and Purification·G A KeeslerH S Lichenstein
Apr 15, 2000·Nature·B B Lowell, B M Spiegelman
Mar 10, 2001·Cell·B M Spiegelman, J S Flier
Oct 30, 2001·The Proceedings of the Nutrition Society·P Trayhurn, J H Beattie
Jan 13, 2004·Physiological Reviews·Barbara Cannon, Jan Nedergaard
May 5, 2005·Genes & Development·Felix B EngelMark T Keating
May 27, 2006·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Meijing WangDaniel R Meldrum
May 3, 2007·American Journal of Physiology. Endocrinology and Metabolism·Jan NedergaardBarbara Cannon
Nov 28, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Melissa R JunttilaJukka Westermarck
Apr 10, 2009·The New England Journal of Medicine·Aaron M CypessC Ronald Kahn
Jul 25, 2009·Nature Reviews. Cancer·Erwin F Wagner, Angel R Nebreda
Jul 30, 2009·American Journal of Physiology. Endocrinology and Metabolism·Owen P McGuinnessDavid H Wasserman
Dec 3, 2010·The Journal of Clinical Investigation·Patrick SealeBruce M Spiegelman
Feb 7, 2012·The Journal of Clinical Investigation·Marica BordicchiaSheila Collins
Jan 17, 2013·Diabetes·Kevin Y LeeC Ronald Kahn
Feb 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Shu-Wen QianQi-Qun Tang
Feb 8, 2013·Genes & Development·Jun WuBruce M Spiegelman
Apr 23, 2013·Nature Medicine·Martin E LidellSven Enerbäck
Dec 3, 2013·Cell Reports·Irina G ShabalinaJan Nedergaard
Feb 18, 2014·Nature Medicine·Benjamin D CosgroveHelen M Blau
Jun 6, 2014·Nature·Vivian PeirceAntonio Vidal-Puig
Aug 26, 2014·Annual Review of Pharmacology and Toxicology·Alexander Pfeifer, Linda S Hoffmann
Nov 26, 2014·Nature Communications·Zhiguo ZhangGuang Ning
Jan 18, 2015·Journal of Hepatology·Yanyan JingHao Ying
Aug 6, 2015·Cell Metabolism·Labros S SidossisDavid N Herndon
Apr 6, 2016·Nature Communications·Kazuki HattoriHidenori Ichijo
Aug 4, 2016·Polish Journal of Veterinary Sciences·J KuryszkoG Sapikowski
Jan 23, 2017·Biochimie·Anastasia V KalinovichJan Nedergaard

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Citations

Apr 30, 2019·Molecular Nutrition & Food Research·Xuan T TruongTae-Il Jeon
Feb 16, 2019·Frontiers in Physiology·Ferran ComasJosé María Moreno-Navarrete
Sep 3, 2020·Biomolecules·Toufic Kassouf, Grzegorz Sumara
Apr 27, 2019·Animals : an Open Access Journal From MDPI·Ting ZhangJunxing Zhao
Oct 18, 2020·Nature Reviews. Endocrinology·Ivana NikolicGuadalupe Sabio
Jan 12, 2021·Frontiers in Endocrinology·Magdalena LeivaGuadalupe Sabio
Jan 29, 2021·Nature Reviews. Molecular Cell Biology·Begoña Canovas, Angel R Nebreda

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Methods Mentioned

BETA
electron microscopy
PCR
immunoprecipitation
ChIP
ELISA
fluorescence microscopy
electrophoresis
Flow cytometry
reverse transcription PCR

Software Mentioned

Image J
Excel

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