S-Nitrosoglutathione Reductase Dysfunction Contributes to Obesity-Associated Hepatic Insulin Resistance via Regulating Autophagy.

Diabetes
Qingwen QianLing Yang

Abstract

Obesity is associated with elevated intracellular nitric oxide (NO) production, which promotes nitrosative stress in metabolic tissues such as liver and skeletal muscle, contributing to insulin resistance. The onset of obesity-associated insulin resistance is due, in part, to the compromise of hepatic autophagy, a process that leads to lysosomal degradation of cellular components. However, it is not known how NO bioactivity might impact autophagy in obesity. Here, we establish that S-nitrosoglutathione reductase (GSNOR), a major protein denitrosylase, provides a key regulatory link between inflammation and autophagy, which is disrupted in obesity and diabetes. We demonstrate that obesity promotes S-nitrosylation of lysosomal proteins in the liver, thereby impairing lysosomal enzyme activities. Moreover, in mice and humans, obesity and diabetes are accompanied by decreases in GSNOR activity, engendering nitrosative stress. In mice with a GSNOR deletion, diet-induced obesity increases lysosomal nitrosative stress and impairs autophagy in the liver, leading to hepatic insulin resistance. Conversely, liver-specific overexpression of GSNOR in obese mice markedly enhances lysosomal function and autophagy and, remarkably, improves ins...Continue Reading

References

Jan 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J S StamlerJ Loscalzo
Jan 1, 1967·Annual Review of Medicine·G Weissmann
Mar 27, 2001·Nature Reviews. Molecular Cell Biology·Y Ohsumi
May 15, 2001·The Journal of Biological Chemistry·V V VaidyanathanP A Roche
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·T Harder, M Kuhn
Jan 22, 2005·Science·Bradford B Lowell, Gerald I Shulman
Feb 3, 2005·Nature Reviews. Molecular Cell Biology·Douglas T HessJonathan S Stamler
Dec 15, 2006·Nature·Gökhan S Hotamisligil
Dec 22, 2006·The Journal of Biological Chemistry·Sovan SarkarDavid C Rubinsztein
Dec 23, 2006·Antioxidants & Redox Signaling·Masao KanekiKyungho Chang
Jul 21, 2007·Nature Protocols·Behrad DerakhshanSteven S Gross
Sep 17, 2008·Clinical Biochemistry·Saleh Zahedi AslFereidoun Azizi
Dec 23, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Hua YuanRoberta A Gottlieb
Feb 14, 2009·Circulation Research·Wim Martinet, Guido R Y De Meyer
Apr 3, 2009·Nature·Rajat SinghMark J Czaja
Apr 16, 2009·Diabetologia·M MasiniP Marchetti
Apr 28, 2009·American Journal of Respiratory and Critical Care Medicine·Loretta G QueMonica Kraft
Sep 10, 2009·Nature Reviews. Molecular Cell Biology·Moran BenharJonathan S Stamler
Dec 1, 2009·Cell Metabolism·Eva MasieroMarco Sandri
Feb 11, 2010·Cell·Noboru MizushimaBeth Levine
Apr 9, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hiroshi KogaAna Maria Cuervo
Jun 4, 2010·Cell Metabolism·Ling YangGökhan S Hotamisligil
Jul 22, 2010·Autophagy·Hiroshi KogaAna Maria Cuervo
Aug 14, 2010·Molecular Cell·Sébastien ThibeaultJean-Philippe Gratton
Nov 5, 2010·The Journal of Clinical Endocrinology and Metabolism·Julia KovsanAssaf Rudich
Jul 6, 2011·Molecular Cell·Sovan SarkarDavid C Rubinsztein
Aug 2, 2011·Cell Metabolism·Susmita KaushikRajat Singh
Aug 23, 2011·Biochemical and Biophysical Research Communications·Yoshihiro InamiSumio Watanabe
Mar 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Farideh BeigiJoshua M Hare
Jun 5, 2012·Journal of Biochemistry·Masaaki Komatsu
Jan 3, 2013·Science Signaling·Paschalis-Thomas DouliasHarry Ischiropoulos
Feb 15, 2013·The New England Journal of Medicine·Augustine M K ChoiBeth Levine
May 10, 2013·The New England Journal of Medicine·Andrea DoriaLeonardo Punzi
May 28, 2013·Biochemical Pharmacology·Minghua YangDaolin Tang
May 28, 2013·Nature Medicine·Edward T ChouchaniMichael P Murphy
Jul 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Durga N TripathiGerald N Wogan
Dec 5, 2013·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Yuka FukuoSumio Watanabe
Jan 15, 2014·Journal of Nutritional Science and Vitaminology·Chikako AraiShigeharu Fukuda
Apr 2, 2014·Antioxidants & Redox Signaling·Costanza MontagnaGiuseppe Filomeni
Dec 23, 2014·Journal of Lipid Research·Bharat JaishyE Dale Abel
Jan 15, 2015·The Journal of Biological Chemistry·Bianca BakerLiwu Li
Mar 18, 2015·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Maki GotoHozumi Motohashi

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Citations

Apr 24, 2018·Liver International : Official Journal of the International Association for the Study of the Liver·Xiaojuan ChaoWen-Xing Ding
Oct 26, 2018·Cancer Chemotherapy and Pharmacology·Chao-Yue SunBing Feng
Mar 29, 2019·International Journal of Molecular Sciences·Serena De MatteisAndrea Casadei-Gardini
Jan 15, 2020·Antioxidants & Redox Signaling·Costanza MontagnaGiuseppe Filomeni
Jan 24, 2018·Diabetes·Kezhong Zhang
Feb 6, 2020·Cell Death & Disease·Kalhara R MenikdiwelaNaima Moustaid-Moussa
Jan 18, 2020·Oxidative Medicine and Cellular Longevity·Lin ZhaoJiankang Liu
May 19, 2020·Chronobiology International·Natalia Kurhaluk, Halyna Tkachenko
Oct 6, 2020·The Biochemical Journal·Salvatore Rizza, Giuseppe Filomeni
Oct 3, 2020·Trends in Plant Science·Baohai LiWolfgang Busch
Sep 25, 2019·Antioxidants & Redox Signaling·Chun-Tao YangMing Xian
Feb 10, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Bulbul AhmedMichael W Greene
Jul 20, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rüdiger Hardeland

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