Insulin-like growth factor-I, inflammatory proteins, and fibrosis in subjects with nonalcoholic fatty liver disease

J Clin Endocrinol Metab. 2013 Feb;98(2):E304-8. doi: 10.1210/jc.2012-3290. Epub 2013 Jan 11.


Context: Inflammation may have a pathogenic role in the progression of nonalcoholic fatty liver disease (NAFLD); by contrast, the role of anti-inflammatory molecules has not been addressed. Low circulating levels of the anti-inflammatory molecule IGF-I have been described in subjects with NAFLD.

Objective: The aim of the study was to elucidate the clinical significance of IGF-I in NAFLD and its relationship with inflammatory biomarkers and fibrosis.

Design and setting: We conducted a cross-sectional study and in vitro experiments on hepatic HepG2 cells at the Internal Medicine and Gastrointestinal and Liver Units of the Universities of Catanzaro and Palermo.

Subjects: A total of 221 individuals with NAFLD diagnosed on ultrasonography (cohort 1) and 50 subjects with biopsy-proven NAFLD (cohort 2) participated in the study.

Intervention: Liver ultrasonography was performed on cohort 1, and hepatic biopsies were obtained from cohort 2.

Main outcome measures: NAFLD fibrosis and Kleiner scores were calculated. IGF-I and inflammatory biomarker plasma concentrations were assessed with specific assays. In the in vitro study, real-time RT-PCR was used to assess the mRNA expression levels of acute-phase reactants.

Results: In the first cohort, circulating IGF-I levels showed an inverse correlation with NAFLD fibrosis score and inflammatory biomarkers; similarly in the second cohort, liver IGF-I mRNA levels and the fibrosis score showed a negative relationship. Finally, we showed that IGF-I was able to directly modulate the expression of acute-phase reactants, decreasing C-reactive protein and fibrinogen levels and up-regulating albumin expression in HepG2 cells.

Conclusions: The present data suggest that evaluation of circulating IGF-I and proinflammatory markers might be useful to assess comprehensively the severity of the disease in individuals with NAFLD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Cell Line
  • Cross-Sectional Studies
  • Fatty Liver / blood*
  • Fatty Liver / diagnostic imaging
  • Fatty Liver / pathology
  • Female
  • Fibrosis
  • Humans
  • Inflammation / blood*
  • Inflammation / diagnostic imaging
  • Inflammation / pathology
  • Insulin-Like Growth Factor I / metabolism*
  • Liver / diagnostic imaging
  • Liver / pathology
  • Male
  • Middle Aged
  • Ultrasonography


  • Biomarkers
  • Insulin-Like Growth Factor I