Stearoyl-CoA desaturase 1 deficiency protects mice from immune-mediated liver injury

Lab Invest. 2009 Feb;89(2):222-30. doi: 10.1038/labinvest.2008.105. Epub 2008 Nov 10.

Abstract

Immunity and metabolism are closely linked. The liver is an important metabolic organ in the body. However, the interactions between hepatocytes and the immune system are poorly understood. In mice developing concanavalin A (ConA)-induced hepatitis (CIH), we found extensive lipid accumulation in hepatocytes. Critical enzyme involved in fat synthesis such as stearoyl-CoA desaturase 1 (SCD1) was upregulated. When we injected ConA to SCD1-deficient mice, we found these mice to be highly resistant to CIH. The mechanisms of the protective effect of SCD1 deficiency might be attributed to the reduced leptin levels in those mice, which modulated critical cytokines and signaling pathways in CIH pathogenesis. In conclusion, our study suggests that SCD1 deficiency protects mice from liver injury in a leptin-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Chemical and Drug Induced Liver Injury / enzymology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Concanavalin A / toxicity
  • Disease Models, Animal
  • Fatty Liver / chemically induced
  • Fatty Liver / enzymology
  • Fatty Liver / pathology
  • Gene Expression / drug effects
  • Hepatocytes / metabolism*
  • Hepatocytes / pathology
  • Leptin / genetics
  • Leptin / metabolism
  • Lipid Metabolism
  • Liver / drug effects
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogens / toxicity
  • NF-kappa B p50 Subunit / metabolism
  • RNA, Messenger / metabolism
  • STAT1 Transcription Factor / metabolism
  • Stearoyl-CoA Desaturase / deficiency*
  • Stearoyl-CoA Desaturase / genetics
  • Up-Regulation

Substances

  • Leptin
  • Mitogens
  • NF-kappa B p50 Subunit
  • RNA, Messenger
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Concanavalin A
  • Nfkb1 protein, mouse
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase