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.
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.
Authors: Giorgio Sesti; Angela Sciacqua; Teresa Vanessa Fiorentino; Maria Perticone; Elena Succurro; Francesco Perticone Journal: PLoS One Date: 2014-08-11 Impact factor: 3.240
Authors: Andre Sarmento-Cabral; Mercedes Del Rio-Moreno; Mari C Vazquez-Borrego; Mariyah Mahmood; Elena Gutierrez-Casado; Natalie Pelke; Grace Guzman; Papasani V Subbaiah; Jose Cordoba-Chacon; Shoshana Yakar; Rhonda D Kineman Journal: J Endocrinol Date: 2021-01 Impact factor: 4.286
Authors: Takara L Stanley; Lindsay T Fourman; Isabel Zheng; Colin M McClure; Meghan N Feldpausch; Martin Torriani; Kathleen E Corey; Raymond T Chung; Hang Lee; David E Kleiner; Colleen M Hadigan; Steven K Grinspoon Journal: J Clin Endocrinol Metab Date: 2021-01-23 Impact factor: 5.958