Regulation of T cell-mediated hepatic inflammation by adiponectin and leptin

Endocrinology. 2005 May;146(5):2157-64. doi: 10.1210/en.2004-1572. Epub 2005 Jan 27.

Abstract

Concanavalin A-induced hepatotoxicity was compared in lipodystrophic aP2-nSREBP-1c transgenic mice (LD mice) lacking adipose tissue, obese leptin-deficient ob/ob mice, and lean wild-type (WT) mice. Serum leptin and adiponectin were low in LD mice, whereas ob/ob mice had undetectable leptin, but high adiponectin. Protection from hepatotoxicity was observed in ob/ob, but not in LD mice, despite low cytokine levels and reduced T cell activation and hepatic natural killer T cells in both groups. Administration of adiponectin protected LD mice from hepatotoxicity without altering cytokine levels. In contrast, administration of leptin heightened disease susceptibility by restoring cytokine production. Neutralization of TNF alpha protected LD mice from liver damage. Increased in vivo susceptibility to the hepatotoxic effect of TNF alpha was observed in LD mice. In vitro, adiponectin protected primary hepatocytes from TNF alpha-induced death, whereas leptin had no protective effect. In conclusion, although leptin increases susceptibility to hepatotoxicity by regulating cytokine production and T cell activation, adiponectin protects hepatocytes from TNF alpha-induced death.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adiponectin
  • Animals
  • Apoptosis
  • Autoimmune Diseases / chemically induced
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Concanavalin A
  • Cytokines / biosynthesis
  • DNA-Binding Proteins / genetics
  • Hepatitis / immunology*
  • In Situ Nick-End Labeling
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Killer Cells, Natural / immunology
  • Leptin / blood
  • Leptin / deficiency
  • Leptin / pharmacology
  • Leptin / physiology*
  • Lipodystrophy / genetics
  • Lipodystrophy / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Obese
  • Mice, Transgenic
  • Obesity / immunology
  • Sterol Regulatory Element Binding Protein 1
  • T-Lymphocytes / immunology*
  • Transcription Factors / genetics
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Adiponectin
  • CCAAT-Enhancer-Binding Proteins
  • Cytokines
  • DNA-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • Leptin
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Concanavalin A