Somatotropic Axis Dysfunction in Non-Alcoholic Fatty Liver Disease: Beneficial Hepatic and Systemic Effects of Hormone Supplementation

Int J Mol Sci. 2018 May 2;19(5):1339. doi: 10.3390/ijms19051339.


Background: Somatotropic axis dysfunction associated with non-alcoholic fatty liver disease (NAFLD) has potential multisystemic detrimental effects. Here, we analysed the effects of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) supplementation on liver histology, adipokine profile and muscle function in an NAFLD model.

Methods: C57BL/6 mice were fed with a high fat diet (HFD) for 12 weeks and were separated into three groups treated for 4 weeks with: (1) High fat diet (HFD) (n = 10); (2) HFD + GH 9 μg/g/d (n = 10); (3) HFD + IGF-1 0.02 µg/g/d (n = 9). A control group fed a chow diet was included (n = 6). Liver histology, liver triglycerides content, serum alanine aminotransferase (ALT) activity, adiponectin and leptin serum levels, in vivo muscle strength, tetanic force and muscle fibre cross-sectional area (CSA) were measured.

Results: HFD + GH and HFD + IGF-1 groups showed significantly lower ALT activity compared to HFD (p < 0.01). Liver triglyceride content in HFD + GH was decreased compared to HFD (p < 0.01). Histologic steatosis score was increased in HFD and HFD + GH group (p < 0.01), whereas HFD + IGF-1 presented no difference compared to the chow group (p = 0.3). HFD + GH group presented lower serum leptin and adiponectin levels compared to HFD. GH and IGF-1 supplementation therapy reverted HFD-induced reduction in muscle strength and CSA (sarcopenia).

Conclusions: GH and IGF-1 supplementation induced significant improvement in liver steatosis, aminotransferases and sarcopenia in a diet-induced NAFLD model.

Keywords: IGF-1; fatty liver; growth hormone; insulin growth factor 1; somatotropic axis.

MeSH terms

  • Adiponectin / blood
  • Alanine Transaminase / blood
  • Animals
  • Diet, High-Fat / adverse effects
  • Dietary Supplements*
  • Disease Models, Animal
  • Growth Hormone / administration & dosage
  • Growth Hormone / therapeutic use*
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / therapeutic use*
  • Leptin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Contraction
  • Muscle Strength
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / therapy*
  • Triglycerides / metabolism


  • Adiponectin
  • Leptin
  • Triglycerides
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Alanine Transaminase