ATF3 mediates inhibitory effects of ethanol on hepatic gluconeogenesis

Proceedings of the National Academy of Sciences of the United States of America
Wen-Wei TsaiMarc R Montminy

Abstract

Increases in circulating glucagon during fasting maintain glucose balance by stimulating hepatic gluconeogenesis. Acute ethanol intoxication promotes fasting hypoglycemia through an increase in hepatic NADH, which inhibits hepatic gluconeogenesis by reducing the conversion of lactate to pyruvate. Here we show that acute ethanol exposure also lowers fasting blood glucose concentrations by inhibiting the CREB-mediated activation of the gluconeogenic program in response to glucagon. Ethanol exposure blocked the recruitment of CREB and its coactivator CRTC2 to gluconeogenic promoters by up-regulating ATF3, a transcriptional repressor that also binds to cAMP-responsive elements and thereby down-regulates gluconeogenic genes. Targeted disruption of ATF3 decreased the effects of ethanol in fasted mice and in cultured hepatocytes. These results illustrate how the induction of transcription factors with overlapping specificity can lead to cross-coupling between stress and hormone-sensitive pathways.

References

Aug 3, 2001·Nature Reviews. Molecular Cell Biology·B Mayr, M Montminy
Jun 17, 2004·Molecular and Cellular Biology·Matthew G HartmanTsonwin Hai
Mar 15, 2005·Clinics in Liver Disease·Charles S Lieber
Apr 4, 2006·Biochimica Et Biophysica Acta·Charles VinsonElizabeth J Taparowsky
Oct 4, 2006·The Biochemical Journal·Dan LuTsonwin Hai
Mar 4, 2009·Cell Metabolism·Ling QiMarc Montminy
Mar 25, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Dagny SandnesG Hege Thoresen
Dec 18, 2010·Nature·Wen-Wei TsaiMichelle Craig Barton
Feb 25, 2011·Nature Reviews. Molecular Cell Biology·Judith Y Altarejos, Marc Montminy
Jul 5, 2011·Cell Metabolism·Hua V Lin, Domenico Accili
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sam Van de VeldeMarc Montminy
Jul 4, 2012·Free Radical Biology & Medicine·Lili YangArthur I Cederbaum
Oct 30, 2012·Clinics in Liver Disease·Arthur I Cederbaum
Jan 26, 2013·Alcoholism, Clinical and Experimental Research·Shivendra D ShuklaGavin E Arteel
May 15, 2013·Proceedings of the National Academy of Sciences of the United States of America·Wen-Wei TsaiMarc Montminy
Aug 8, 2013·The Journal of Clinical Investigation·Chris C WolfordTsonwin Hai
Sep 21, 2013·The Journal of Clinical Investigation·Kim RavnskjaerMarc Montminy
Apr 5, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Stephanie MathewsBin Gao

❮ Previous
Next ❯

Citations

Feb 23, 2017·Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række·Trond SkjelstadErik Waage Nielsen
Apr 4, 2017·Trends in Genetics : TIG·Caroline C EscoubasWilliam B Mair
May 30, 2015·Journal of Lipid Research·Jin GuYan Chen
Nov 2, 2019·Communications Biology·Ching-Feng ChengHeng Lin
Jul 28, 2020·Frontiers in Oncology·Jacinta Serpa
Jan 12, 2020·Communications Biology·Ching-Feng ChengHeng Lin
Jun 12, 2021·Toxicology and Applied Pharmacology·Jing SunJingqi Fu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Yiguo WangMarc R Montminy
Proceedings of the National Academy of Sciences of the United States of America
Wen-Wei TsaiMarc R Montminy
© 2022 Meta ULC. All rights reserved