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  • Title: Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH/IGF-I levels.
    Author: Fusco A, Miele L, D'Uonnolo A, Forgione A, Riccardi L, Cefalo C, Barini A, Bianchi A, Giampietro A, Cimino V, Landolfi R, Grieco A, De Marinis L.
    Journal: Clin Endocrinol (Oxf); 2012 Oct; 77(4):531-6. PubMed ID: 22077984.
    Abstract:
    INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has been described in adult GH deficiency syndrome. Furthermore, chronic liver disease can be associated with significant changes in levels of IGF-I, GH-binding protein (GHBP), IGF-binding proteins (IGFBPs) and acid-labile subunit (ALS). However, the effect of liver steatosis on the GHBP production has not been investigated yet. AIM OF THE STUDY: To explore whether GH secretion and/or levels of IGF-I, IGFBP-3, ALS and GHBP could be altered in obese patients in relation to the presence of liver steatosis. MATERIALS AND METHODS: A total of 115 obese patients (BMI > 30) were enrolled in the protocol (65 patients with liver steatosis and 50 age- and BMI-matched controls). In all patients, the following parameters were studied: serum levels of glucose, insulin, the HOMA index, IGF-I, GHBP, IGFBP-3, ALS and GH after GHRH and arginine stimulation test. RESULTS: As expected, patients with NAFLD had blood glucose, insulin, HOMA-R significantly higher than controls, indicating a more severe insulin-resistance state in NAFLD. Furthermore, patients with NAFLD had higher levels of GHBP and IGFBP-3 and lower GH peak and IGF-I levels as compared to controls. No difference was found in ALS levels between the groups. In a multivariate analysis, GHBP was positively associated with hepatic steatosis while IGF-1 was negatively associated with hepatic steatosis. CONCLUSIONS: This study demonstrates that in patients with NAFLD, the GHBP levels are increased, and that the GH/IGF-I axis is significantly altered probably leading to reduced IGF-I bioavailability at tissue level.
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