Myeloid-specific SIRT1 Deletion Aggravates Hepatic Inflammation and Steatosis in High-fat Diet-fed Mice

The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
Kyung Eun KimGu Seob Roh

Abstract

Sirtuin 1 (SIRT1) is a mammalian NAD(+)-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-κB), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle ac...Continue Reading

References

Mar 21, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·G Svegliati BaroniA Benedetti
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·J S SmithJ D Boeke
Apr 5, 2001·American Journal of Physiology. Endocrinology and Metabolism·P A KernG Ranganathan
Oct 5, 2001·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·V ParadisP Bedossa
Jan 13, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·M den BoerJ A Romijn
Mar 2, 2005·The European Respiratory Journal·P J BarnesK Ito
Mar 3, 2007·The Journal of Clinical Investigation·John P Iredale
May 15, 2007·Liver International : Official Journal of the International Association for the Study of the Liver·Xiang-Qun DengNing-Xu Li
Jun 21, 2007·American Journal of Physiology. Endocrinology and Metabolism·Bart M De TaeyeDouglas E Vaughan
Jul 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Joseph T Rodgers, Pere Puigserver
Jan 5, 2008·American Journal of Respiratory and Critical Care Medicine·Saravanan RajendrasozhanIrfan Rahman
Jul 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Paul T PflugerMatthias H Tschöp
Dec 24, 2008·Molecular and Cellular Biology·Takeshi YoshizakiJerrold M Olefsky
Dec 10, 2009·American Journal of Physiology. Endocrinology and Metabolism·Takeshi YoshizakiJerrold M Olefsky
Dec 17, 2009·Genes & Development·Dena E CohenLeonard P Guarente
Feb 13, 2010·Annual Review of Physiology·Jerrold M Olefsky, Christopher K Glass
May 29, 2010·Circulation Research·Ajay Chawla
Jul 22, 2010·Molecular and Cellular Biology·Thaddeus T SchugXiaoling Li
Oct 19, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aparna PurushothamXiaoling Li
Mar 21, 2012·Nature Reviews. Neuroscience·Ana M Fernandez, Ignacio Torres-Alemán
Dec 22, 2012·Acta Biochimica Et Biophysica Sinica·Xiaoling Li
Sep 2, 2014·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Seok KimGu Seob Roh

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Citations

Apr 20, 2016·Expert Review of Gastroenterology & Hepatology·Fa-Ling WuMing-Hua Zheng
Dec 29, 2016·World Journal of Gastroenterology : WJG·Fatiha Nassir, Jamal A Ibdah
Dec 13, 2016·Cellular and Molecular Life Sciences : CMLS·Javier Traba, Michael N Sack
Mar 9, 2018·BioMed Research International·Francesca BonominiRita Rezzani
Nov 21, 2020·Expert Review of Gastroenterology & Hepatology·Shifeng FuDengliang Liu

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Methods Mentioned

BETA
genotyping
ELISA
acetylation
nuclear translocation

Software Mentioned

Gauge
Multi
- FIVE
analySIS

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