Nonalcoholic fatty liver disease is associated with low circulating levels of insulin-like growth factor-I

J Clin Endocrinol Metab. 2011 Oct;96(10):E1640-4. doi: 10.1210/jc.2011-1227. Epub 2011 Aug 3.


Context: 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.

Main outcome measures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / physiology
  • Anthropometry
  • Cardiovascular Diseases / diagnostic imaging
  • Cardiovascular Diseases / epidemiology
  • Cell Line, Tumor
  • Cross-Sectional Studies
  • Dose-Response Relationship, Drug
  • Fatty Acids, Nonesterified / blood
  • Fatty Liver / blood*
  • Fatty Liver / diagnostic imaging
  • Female
  • Humans
  • Insulin Resistance
  • Insulin-Like Growth Factor I / deficiency*
  • Insulin-Like Growth Factor I / metabolism*
  • Lipids / blood
  • Male
  • Metabolic Diseases / diagnostic imaging
  • Metabolic Diseases / epidemiology
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Receptors, Somatotropin / drug effects
  • Risk Factors
  • Sex Characteristics
  • Ultrasonography


  • Fatty Acids, Nonesterified
  • Lipids
  • Receptors, Somatotropin
  • Insulin-Like Growth Factor I