Nonalcoholic fatty liver disease is associated with low circulating levels of insulin-like growth factor-I
F Arturi, E Succurro, C Procopio… - The Journal of …, 2011 - academic.oup.com
The Journal of Clinical Endocrinology & Metabolism, 2011•academic.oup.com
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 …
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 …
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.
Oxford University Press