Insulin-Like Growth Factor-I, Inflammatory Proteins, and Fibrosis in Subjects With Nonalcoholic Fatty Liver Disease

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 2; pp. E304 - E308
• Main Authors: Hribal, Marta Letizia, Procopio, Teresa, Petta, Salvatore, Sciacqua, Angela, Grimaudo, Stefania, Pipitone, Rosaria Maria, Perticone, Francesco, Sesti, Giorgio
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.02.2013; Copyright by The Endocrine Society
• Subjects: Aged; Biomarkers; Biomarkers - blood; Biopsy; C-reactive protein; Cell Line; Cross-Sectional Studies; Fatty liver; Fatty Liver - blood; Fatty Liver - diagnostic imaging; Fatty Liver - pathology; Female; Fibrinogen; Fibrosis; Gene expression; Hepatocytes; Humans; Inflammation - blood; Inflammation - diagnostic imaging; Inflammation - pathology; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factors; Liver - diagnostic imaging; Liver - pathology; Liver diseases; Male; Middle Aged; Ultrasonic imaging; Ultrasonography
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2012-3290

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.