Accumulation of succinate controls activation of adipose tissue thermogenesis.

Nature
Evanna MillsEdward T Chouchani

Abstract

Thermogenesis by brown and beige adipose tissue, which requires activation by external stimuli, can counter metabolic disease1. Thermogenic respiration is initiated by adipocyte lipolysis through cyclic AMP-protein kinase A signalling; this pathway has been subject to longstanding clinical investigation2-4. Here we apply a comparative metabolomics approach and identify an independent metabolic pathway that controls acute activation of adipose tissue thermogenesis in vivo. We show that substantial and selective accumulation of the tricarboxylic acid cycle intermediate succinate is a metabolic signature of adipose tissue thermogenesis upon activation by exposure to cold. Succinate accumulation occurs independently of adrenergic signalling, and is sufficient to elevate thermogenic respiration in brown adipocytes. Selective accumulation of succinate may be driven by a capacity of brown adipocytes to sequester elevated circulating succinate. Furthermore, brown adipose tissue thermogenesis can be initiated by systemic administration of succinate in mice. Succinate from the extracellular milieu is rapidly metabolized by brown adipocytes, and its oxidation by succinate dehydrogenase is required for activation of thermogenesis. We ident...Continue Reading

References

Feb 23, 1978·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·J L BrowneD H Smyth
Sep 23, 1976·European Journal of Applied Physiology and Occupational Physiology·P W Hochachka, R H Dressendorfer
Apr 1, 1990·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·A MaekawaY Hayashi
Jan 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hiroko MiyaderaSatoshi Omura
Apr 6, 2006·American Journal of Physiology. Endocrinology and Metabolism·Valeria GolozoubovaJan Nedergaard
May 1, 1968·The Biochemical Journal·R HemsH A Krebs
Jan 1, 1928·The Biochemical Journal·J H Quastel, W R Wooldridge
Apr 25, 2007·Journal of Hepatology·Paulo Renato A V CorreaMichael H Nathanson
Dec 9, 2008·The Biochemical Journal·Michael P Murphy
Jul 24, 2010·Annals of the New York Academy of Sciences·Robin A J Smith, Michael P Murphy
Dec 24, 2010·The Journal of Experimental Biology·Barbara Cannon, Jan Nedergaard
Dec 25, 2010·Cell·Edward L HuttlinSteven P Gygi
Jul 6, 2011·The Biochemical Journal·Martin D Brand, David G Nicholls
Jun 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Aaron M CypessC Ronald Kahn
Jul 4, 2012·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Y RavussinR L Leibel
Oct 16, 2012·Diabetologia·A L CareyB A Kingwell
Jul 31, 2013·Clinical Chemistry·Mary K TownsendBrian M Wolpin
Nov 1, 1994·Journal of the American Society for Mass Spectrometry·J K EngJ R Yates
Aug 26, 2014·Annual Review of Pharmacology and Toxicology·Alexander Pfeifer, Linda S Hoffmann
Jan 8, 2015·Cell Metabolism·Aaron M CypessGerald M Kolodny
Mar 17, 2015·Nature Medicine·Kosaku ShinodaShingo Kajimura
Sep 15, 2015·Nature Chemical Biology·Adam L OrrMartin D Brand
Mar 31, 2016·Nature·Edward T ChouchaniBruce M Spiegelman
Aug 3, 2016·The Journal of Experimental Medicine·Amanda Littlewood-EvansJosé M Carballido
Aug 10, 2016·Nature Communications·Johannes K EhingerEskil Elmér
Aug 27, 2017·The Journal of Biological Chemistry·Edward T ChouchaniBruce M Spiegelman
Oct 7, 2017·Cell·Brandon FaubertRalph J DeBerardinis
Oct 19, 2017·Nature·Sheng HuiJoshua D Rabinowitz

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Citations

Dec 21, 2018·Obesity·Suzanne N Shapira, Patrick Seale
Feb 7, 2019·Physiology·Magdalene K MontgomeryMatthew J Watt
Jan 4, 2019·The Plant Journal : for Cell and Molecular Biology·Shaobai HuangA Harvey Millar
Jul 19, 2019·EMBO Reports·Tao WangQing-Yan Jiang
Aug 6, 2019·Scandinavian Journal of Immunology·Jacek Hawiger, Jozef Zienkiewicz
Oct 2, 2019·The Journal of Clinical Investigation·Anying SongQiong A Wang
Oct 28, 2019·Reviews in Endocrine & Metabolic Disorders·Sonia Fernández-Veledo, Joan Vendrell
Jan 16, 2020·Biomolecules·Petr JežekLydie Plecitá-Hlavatá
Jan 4, 2020·Journal of Physiology and Biochemistry·Audrey CarrièreLouis Casteilla
Feb 15, 2020·The Biochemical Journal·Anna Roesler, Lawrence Kazak
Jan 7, 2020·The Journal of Clinical Endocrinology and Metabolism·Zahraa Abdul SaterAaron M Cypess
Aug 20, 2019·EMBO Reports·Judit Castillo-ArmengolIsabel C Lopez-Mejia
Jan 5, 2020·Nature Communications·Inmaculada Martínez-Reyes, Navdeep S Chandel
Jun 1, 2020·Journal of Physiology and Biochemistry·María J Moreno-Aliaga, Francesc Villarroya
Jun 6, 2020·Antioxidants·Ryan J Mailloux
Aug 9, 2020·Cardiovascular Research·Hiran A PragDunja Aksentijević
Aug 18, 2020·American Journal of Physiology. Endocrinology and Metabolism·Pradip K SahaSean M Hartig
Apr 30, 2019·Nature Metabolism·Dylan G RyanEvanna L Mills
May 22, 2019·Journal of Clinical Medicine·Vincent Cuminetti, Lorena Arranz
Aug 4, 2019·Diabetes Care·Victoria Ceperuelo-MallafréSonia Fernández-Veledo
Oct 23, 2019·Signal Transduction and Targeted Therapy·Ziying ZhangYongguang Tao
Jan 7, 2020·Nature Metabolism·Edward T Chouchani, Shingo Kajimura
Apr 3, 2020·Journal of Physiology and Biochemistry·A RodríguezSara Becerril
Apr 18, 2020·The FEBS Journal·Mohammed Faiz HussainLawrence Kazak
Jun 20, 2020·Proceedings of the National Academy of Sciences of the United States of America·Mengxi JiangNai-Jia Huang
Sep 19, 2020·Nature Metabolism·Rebeca Acín-PérezJosé Antonio Enríquez
Sep 27, 2018·Intensive Care Medicine Experimental·Alessandro Protti
May 23, 2019·Nature Reviews. Immunology·Christoph SchneiderRichard M Locksley
Aug 23, 2019·Physiological Reviews·David S Wishart
Mar 27, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yan ChenJiang Wei Wu
Apr 16, 2020·Redox Report : Communications in Free Radical Research·Katerina Hadrava VanovaJakub Rohlena
Jun 5, 2020·Nature Reviews. Endocrinology·Lawrence Kazak, Paul Cohen
Feb 15, 2019·Frontiers in Physiology·Shireesh Srivastava, Richard L Veech
Oct 17, 2019·International Journal of Molecular Sciences·Fernando Lizcano
Jun 30, 2019·Oxidative Medicine and Cellular Longevity·Lydie Plecitá-HlavatáPetr Ježek

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