Nonalcoholic fatty liver disease is associated with increased GHBP and reduced GH/IGF-I levels

Clin Endocrinol (Oxf). 2012 Oct;77(4):531-6. doi: 10.1111/j.1365-2265.2011.04291.x.

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.

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Carrier Proteins / blood*
  • Cross-Sectional Studies
  • Fatty Liver / blood*
  • Female
  • Glycoproteins / blood
  • Growth Hormone / blood*
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / blood
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Obesity / blood

Substances

  • Blood Glucose
  • Carrier Proteins
  • Glycoproteins
  • Insulin-Like Growth Factor Binding Proteins
  • insulin-like growth factor binding protein, acid labile subunit
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • somatotropin-binding protein