title: Nonalcoholic fatty liver disease is associated with low circulating levels of insulin-like growth factor-I.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is associated with insulin resistance and cardiovascular disease. Among the potential factors that may account for the increased cardiometabolic risk, IGF-I is a plausible candidate because the liver is the main site of its production.
  
  
  OBJECTIVE
  Our objective was to examine the relationship between NAFLD and IGF-I levels and to test the hypothesis that free fatty acids-induced insulin resistance might impair insulin-induced increase of GH receptor (GHR) expression in human hepatoma cells. SUBJECTS, DESIGN, AND SETTING: Five hundred three nondiabetic Caucasians participated in this ambulatory-care cross-sectional study.
  
  
  METHODS
  Cardiometabolic risk factors and liver ultrasound scanning were assessed. Insulin-induced expression of GHR in HuH7 human hepatoma cells exposed for 24 h to palmitate was determined by Western blotting and real-time PCR.
  
  
  RESULTS
  After adjustment for age and gender, individuals with NAFLD had significantly higher body mass index, waist circumference, fasting insulin, triglycerides, homeostasis model assessment index, liver enzymes, and lower high-density lipoprotein cholesterol compared with control subjects. IGF-I levels were significantly lower in individuals with NAFLD (P = 0.001). Exposure of HuH7 hepatoma cells to palmitate caused a dose-dependent reduction in the insulin-induced increase of GHR expression.
  
  
  CONCLUSIONS
  These data show that IGF-I levels are reduced in subjects with NAFLD and suggest that hepatic insulin resistance may affect IGF-I levels by modulating GH-stimulated synthesis of hepatic IGF-I.
authors.affiliation: Dipartimento Medicina Sperimentale e Clinica, Università Magna-Graecia di Catanzaro, Viale Europa, 88100 Catanzaro, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Arturi
authors.forename: Elena
authors.initials: E
authors.lastname: Succurro
authors.forename: Cristina
authors.initials: C
authors.lastname: Procopio
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pedace
authors.forename: Gaia Chiara
authors.initials: GC
authors.lastname: Mannino
authors.forename: Marina
authors.initials: M
authors.lastname: Lugarà
authors.forename: Teresa
authors.initials: T
authors.lastname: Procopio
authors.forename: Francesco
authors.initials: F
authors.lastname: Andreozzi
authors.forename: Angela
authors.initials: A
authors.lastname: Sciacqua
authors.forename: Marta Letizia
authors.initials: ML
authors.lastname: Hribal
authors.forename: Francesco
authors.initials: F
authors.lastname: Perticone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology; D000886:Anthropometry; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology; D045744:Cell Line, Tumor; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000097:blood* / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D008659:Metabolic Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D011986:Receptors, Somatotropin / Q000187:drug effects; D012307:Risk Factors; D012727:Sex Characteristics; D014463:Ultrasonography
chemical_list: D005230:Fatty Acids, Nonesterified; D008055:Lipids; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I