Adiponectin upregulates hepatocyte CMKLR1 which is reduced in human fatty liver

Mol Cell Endocrinol. 2012 Feb 26;349(2):248-54. doi: 10.1016/j.mce.2011.10.032. Epub 2011 Nov 18.

Abstract

Chemokine-like receptor 1 (CMKLR1) ligands chemerin and resolvin E1 are suggested to have a role in non-alcoholic fatty liver disease (NAFLD). Here, expression of CMKLR1 in liver cells and NAFLD was studied. CMKLR1 was detected in primary human hepatocytes (PHH), Kupffer cells, bile-duct cells and hepatic stellate cells. In human and rodent fatty liver and in fibrotic liver of mice fed a methionine-choline deficient diet CMKLR1 was reduced. Hepatocytes are the major cells in the liver and effects of adipokines, cytokines and lipids on CMKLR1 in PHH were analyzed. Increased cellular triglyceride or cholesterol content, lipopolysaccharide, IL-6, TNF and leptin did not influence CMKLR1 levels in PHH whereas profibrotic TGFβ tended to reduce CMKLR1. Adiponectin strongly upregulated CMKLR1 mRNA and protein in PHH and hepatic CMKLR1 when injected into wild type mice. Further, CMKLR1 was suppressed in the liver of adiponectin deficient mice. These data indicate that low CMKLR1 in NAFLD may partly result from reduced adiponectin activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / antagonists & inhibitors
  • Adiponectin / metabolism*
  • Adiponectin / pharmacology
  • Aged
  • Animals
  • Bile Ducts / drug effects
  • Bile Ducts / metabolism*
  • Bile Ducts / pathology
  • Choline / metabolism
  • Diet
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • Female
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Humans
  • Kupffer Cells / drug effects
  • Kupffer Cells / metabolism
  • Kupffer Cells / pathology
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Methionine / deficiency
  • Mice
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Primary Cell Culture
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation

Substances

  • Adiponectin
  • CMKLR1 protein, human
  • RNA, Messenger
  • Receptors, Chemokine
  • Transforming Growth Factor beta
  • Methionine
  • Choline