title: Nitrosative stress predicts the presence and severity of nonalcoholic fatty liver at different stages of the development of insulin resistance and metabolic syndrome: possible role of vitamin A intake.
abstract: BACKGROUND
  Although nonalcoholic fatty liver disease (NAFLD) is associated with the metabolic syndrome, the mechanisms responsible for the development of NAFLD at different stages of the development of insulin resistance are unknown. Diet, adipokines, and nitrosative stress have been linked to both NAFLD and insulin resistance.
  
  
  OBJECTIVE
  We aimed to identify the factors that are specifically associated with NAFLD at different stages in the development of insulin resistance and the metabolic syndrome.
  
  
  METHODS
  Circulating concentrations of adipokines (ie, tumor necrosis factor-alpha, adiponectin, resistin, leptin, and interleukin-6), markers of nitrosative stress (nitrotyrosine), dietary habits, and MTP -493G/T polymorphism were cross-sectionally related to the presence and severity of insulin resistance (homeostasis model assessment index for insulin resistance: >or=2), the metabolic syndrome, and fatty liver in 64 nonobese nondiabetic patients with NAFLD (33 insulin-sensitive and 31 insulin-resistant subjects) and 74 control subjects without liver disease who were matched for sex, BMI, homeostasis model assessment index for insulin resistance status, and the various features of the metabolic syndrome.
  
  
  RESULTS
  Persons with NAFLD had greater systemic nitrosative stress and a lower intake of vitamins A and E than did control subjects, but the 2 groups did not differ significantly in any other features. Nitrotyrosine and adiponectin concentrations and vitamin A intakes independently predicted alanine aminotransferase concentrations in NAFLD patients and liver histology in a subgroup of 29 subjects with biopsy-proven nonalcoholic steatohepatitis.
  
  
  CONCLUSIONS
  Oxidative stress is operating in NAFLD and nonalcoholic steatohepatitis, even in the absence of insulin resistance, the metabolic syndrome, and hypoadiponectinemia, which aggravate liver histology at more severe stages of metabolic disease. The possible pathogenetic role of reduced vitamin A intake in NAFLD warrants further investigation.
authors.affiliation: Emergency Medicine Department, Gradenigo Hospital, Turin, Italy. giovanni_musso@yahoo.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Musso
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambino
authors.forename: Franco
authors.initials: F
authors.lastname: De Michieli
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Biroli
authors.forename: Alberto
authors.initials: A
authors.lastname: Premoli
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pagano
authors.forename: Simona
authors.initials: S
authors.lastname: Bo
authors.forename: Marilena
authors.initials: M
authors.lastname: Durazzo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cassader
mesh_terms: D054392:Adipokines / Q000097:blood*; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005234:Fatty Liver / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology; D005247:Feeding Behavior; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications* / Q000473:pathology; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D014801:Vitamin A / Q000008:administration & dosage / Q000502:physiology*