Lack of SIRT1 (Mammalian Sirtuin 1) activity leads to liver steatosis in the SIRT1+/- mice: a role of lipid mobilization and inflammation

Endocrinology. 2010 Jun;151(6):2504-14. doi: 10.1210/en.2009-1013. Epub 2010 Mar 25.


Mammalian sirtuin 1 (SIRT1) may control fatty acid homeostasis in liver. However, this possibility and underlying mechanism remain to be established. In this study, we addressed the issues by examining the metabolic phenotypes of SIRT1 heterozygous knockout (SIRT1(+/-)) mice. The study was conducted in the mice on three different diets including a low-fat diet (5% fat wt/wt), mediate-fat diet (11% fat wt/wt), and high-fat diet (HFD, 36% fat wt/wt). On low-fat diet, the mice did not exhibit any abnormality. On mediate-fat diet, the mice exhibited a significant increase in hepatic steatosis with elevated liver/body ratio, liver size, liver lipid (triglyceride, glycerol, and cholesterol) content, and liver inflammation. The hepatic steatosis was deteriorated in the mice by HFD. In the liver, lipogenesis was increased, fat export was reduced, and beta-oxidation was not significantly changed. Body weight and fat content were increased in response to the dietary fat. Fat was mainly increased in sc adipose tissue and liver. Inflammation was also elevated in epididymal fat. Whole body energy expenditure and substrate utilization were reduced. Food intake, locomotor activity, and fat absorption were not changed. These data suggest that a reduction in the SIRT1 activity increases the risk of fatty liver in response to dietary fat. The liver steatosis may be a result of increased lipogenesis and reduced liver fat export. The inflammation may contribute to the pathogenesis of hepatic steatosis as well. A reduction in lipid mobilization may contribute to the hepatic steatosis and low energy expenditure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Fatty Liver / genetics
  • Fatty Liver / immunology*
  • Fatty Liver / metabolism*
  • Genotype
  • Inflammation / genetics
  • Inflammation / physiopathology*
  • Lipid Metabolism / genetics
  • Lipid Metabolism / physiology*
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism*


  • Sirt1 protein, mouse
  • Sirtuin 1