title: Adiponectin upregulates hepatocyte CMKLR1 which is reduced in human fatty liver.
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.
authors: Department of Internal Medicine I, Regensburg University Hospital, Regensburg D-93042, Germany.
authors: Josef
authors: J
authors: Wanninger
authors: Sabrina
authors: S
authors: Bauer
authors: Kristina
authors: K
authors: Eisinger
authors: Thomas S
authors: TS
authors: Weiss
authors: Roland
authors: R
authors: Walter
authors: Claus
authors: C
authors: Hellerbrand
authors: Andreas
authors: A
authors: Schäffler
authors: Akiko
authors: A
authors: Higuchi
authors: Kenneth
authors: K
authors: Walsh
authors: Christa
authors: C
authors: Buechler
mesh_terms: D052242:Adiponectin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000368:Aged; D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002794:Choline / Q000378:metabolism; D004032:Diet; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005260:Female; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008715:Methionine / Q000172:deficiency; D051379:Mice; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; C102741:CMKLR1 protein, human; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta; D008715:Methionine; D002794:Choline