title: Fibrosis is associated with adiponectin resistance in chronic hepatitis C virus infection.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection is frequently associated with insulin resistance which has been suggested to promote fibrotic progression. Adiponectin, an adipocyte-derived insulin-sensitizing hormone, might play a protective role against hepatic fibrosis.
  
  
  METHODS
  This observational case-control study investigated the adiponectin status in insulin resistant, nondiabetic, chronic HCV-infected patients (n=54; 13 women, 41 men) compared with age-, sex- and BMI-matched healthy controls. Liver biopsies from patients with chronic HCV hepatitis were analysed for the adiponectin and adiponectin receptors (ADIPOR) 1 and 2 mRNA and protein expressions.
  
  
  RESULTS
  Serum adiponectin levels were higher in patients with chronic HCV hepatitis than in healthy controls (12·1±4·7 vs. 9·5±4·4 mg L(-1) in men, P = 0·01; 18·2±4·4 vs. 13·6±5·3mgL(-1) in women, P=0·02). BMI, HDL cholesterol and triglycerides levels correlated with adiponectin levels both in patients and in controls, while no correlation with glucose, insulin and HOMA-IR values could be detected. Nonetheless, insulin resistance was predictive of steatosis and fibrosis in chronic HCV-infected patients. Interestingly, patients with none or mild fibrosis showed serum adiponectin levels similar to those in healthy controls, while hyperadiponectinemia was associated with moderate to severe stages of fibrosis. Hyperadiponectinemia was unlikely sustained by liver production as hepatocytes did not express the protein. ADIPOR1 mRNA, but not ADIPOR2 levels, was reduced in chronic HCV hepatitis. The reduced ADIPOR1 expression was confirmed by immunohistochemistry.
  
  
  CONCLUSIONS
  In patients with chronic HCV hepatitis, fibrosis was associated with hyperadiponectinemia. Chronic HCV-infected hepatocytes showed reduced ADIPOR1 expression, suggesting a pattern of adiponectin resistance.
authors.affiliation: Endocrinology and Diabetology Unit, Department of Medical-Surgical Sciences, University of Milan, Milan, Italy. sabrina.corbetta@unimi.it
authors.forename: Sabrina
authors.initials: S
authors.lastname: Corbetta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Redaelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Pozzi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bovo
authors.forename: Laura
authors.initials: L
authors.lastname: Ratti
authors.forename: Elena
authors.initials: E
authors.lastname: Redaelli
authors.forename: Caterina
authors.initials: C
authors.lastname: Pellegrini
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Anna
authors.initials: A
authors.lastname: Spada
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000704:Analysis of Variance; D015992:Body Mass Index; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood*; D006801:Humans; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D008076:Cholesterol, HDL; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D014280:Triglycerides