Rho-kinase/AMPK axis regulates hepatic lipogenesis during overnutrition

The Journal of Clinical Investigation
Hu HuangYoung-Bum Kim

Abstract

Obesity is a major risk factor for developing nonalcoholic fatty liver disease (NAFLD). NAFLD is the most common form of chronic liver disease and is closely associated with insulin resistance, ultimately leading to cirrhosis and hepatocellular carcinoma. However, knowledge of the intracellular regulators of obesity-linked fatty liver disease remains incomplete. Here we showed that hepatic Rho-kinase 1 (ROCK1) drives obesity-induced steatosis in mice through stimulation of de novo lipogenesis. Mice lacking ROCK1 in the liver were resistant to diet-induced obesity owing to increased energy expenditure and thermogenic gene expression. Constitutive expression of hepatic ROCK1 was sufficient to promote adiposity, insulin resistance, and hepatic lipid accumulation in mice fed a high-fat diet. Correspondingly, liver-specific ROCK1 deletion prevented the development of severe hepatic steatosis and reduced hyperglycemia in obese diabetic (ob/ob) mice. Of pathophysiological significance, hepatic ROCK1 was markedly upregulated in humans with fatty liver disease and correlated with risk factors clustering around NAFLD and insulin resistance. Mechanistically, we found that hepatic ROCK1 suppresses AMPK activity and a ROCK1/AMPK pathway is ...Continue Reading

References

Oct 19, 2000·Methods in Enzymology·S NarumiyaM Uehata
Jul 16, 2004·The Journal of Clinical Investigation·Jeffrey D Browning, Jay D Horton
May 3, 2005·The Journal of Clinical Investigation·Douglas Osei-HyiamanGeorge Kunos
Aug 16, 2005·Cell Metabolism·Noboru FurukawaYoung-Bum Kim
Nov 4, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Takeshi KandaTakao Saruta
Nov 23, 2005·Proceedings of the National Academy of Sciences of the United States of America·Daehee HwangLeroy Hood
Sep 1, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hitoshi IkedaYutaka Yatomi
Oct 5, 2007·Journal of Gastroenterology and Hepatology·Kumi KitamuraToshifumi Hibi
Jan 26, 2008·Trends in Molecular Medicine·Fabio MarraClaudio Tiribelli
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Mar 12, 2009·The Journal of Biological Chemistry·Dae Ho LeeYoung-Bum Kim
Dec 31, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Elisa FabbriniSamuel Klein
Jan 15, 2010·The Journal of Biological Chemistry·He-Jin LeeSeung-Jae Lee
May 13, 2010·Digestive Diseases·Stefano BellentaniGiorgio Bedogni
Nov 5, 2010·Diabetes, Obesity & Metabolism·P Ferré, F Foufelle
Apr 21, 2011·American Journal of Physiology. Endocrinology and Metabolism·Nanlan LuoYuchang Fu
May 11, 2011·Nature Reviews. Endocrinology·Briohny W Smith, Leon A Adams
Jun 3, 2011·The Journal of Clinical Investigation·Rexford S Ahima
Nov 29, 2011·Clinical Science·Benoit ViolletFabrizio Andreelli
Jan 19, 2012·JAMA : the Journal of the American Medical Association·Katherine M FlegalCynthia L Ogden
Feb 4, 2012·Genes & Development·Ffolliott M FisherBruce M Spiegelman
Aug 1, 2012·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Ying-Ying YangHan-Chieh Lin
Aug 2, 2012·American Journal of Physiology. Endocrinology and Metabolism·Ana F SoaresJohn G Jones
Jan 23, 2013·Nature Reviews. Endocrinology·Norbert Stefan, Hans-Ulrich Häring
Aug 10, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Andreas L Birkenfeld, Gerald I Shulman
Aug 14, 2013·Trends in Endocrinology and Metabolism : TEM·Hu HuangYoung-Bum Kim
Sep 18, 2013·Nature Reviews. Gastroenterology & Hepatology·Rohit Loomba, Arun J Sanyal
Dec 12, 2013·American Journal of Physiology. Endocrinology and Metabolism·Seung-Hwan LeeYoung-Bum Kim
Jan 1, 2014·Hypertension·Masato KajikawaYukihito Higashi
Jun 10, 2015·JAMA : the Journal of the American Medical Association·Mary E Rinella
Dec 29, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Zobair M YounossiMark Wymer

❮ Previous
Next ❯

Citations

Mar 29, 2019·Journal of Diabetes Investigation·Takafumi MiyamotoHitoshi Shimano
Apr 2, 2020·Journal of Diabetes Investigation·Takashi Matsuzaka, Hitoshi Shimano
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lei WeiJianjian Shi
Jun 12, 2020·Seminars in Liver Disease·Samar H IbrahimGregory J Gores
Feb 8, 2020·Mechanisms of Ageing and Development·Vitor Rosetto MuñozJosé Rodrigo Pauli
Dec 29, 2020·American Journal of Physiology. Endocrinology and Metabolism·Min-Cheol KangYoung-Bum Kim
Dec 25, 2019·Annals of Hepatology·S M Touhidul IslamInderjit Singh
Feb 27, 2021·Frontiers in Endocrinology·Taylor LandryHu Huang
Mar 18, 2021·Cell Reports·Irene AnastasiaLuca Pellegrini
Jul 3, 2021·International Journal of Molecular Sciences·Siarhei A DabravolskiAlexander N Orekhov
Oct 7, 2021·Diabetes & Metabolism Journal·Inês Sousa-LimaYoung-Bum Kim
Jan 5, 2022·Investigative Ophthalmology & Visual Science·Yasushi KitaokaHitoshi Takagi

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE112548

Methods Mentioned

BETA
ELISA
immunoprecipitation
PCR

Software Mentioned

DAVID Bioinformatics Resources
CLAMS
StatView

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.