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

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.