Somatotropic Axis Dysfunction in Non-Alcoholic Fatty Liver Disease: Beneficial Hepatic and Systemic Effects of Hormone Supplementation
Daniel Cabrera, Claudio Cabello-Verrugio, Nancy Solís, Diego San Martín, Catalina Cofré, Margarita Pizarro, Juan Pablo Arab, Johanna Abrigo, Fabián Campos, Betzabé Irigoyen, Gonzalo Carrasco-Avino, Katiuska Bezares, Valentina Riquelme, Arnoldo Riquelme, Marco Arrese, Francisco Barrera, Daniel Cabrera, Claudio Cabello-Verrugio, Nancy Solís, Diego San Martín, Catalina Cofré, Margarita Pizarro, Juan Pablo Arab, Johanna Abrigo, Fabián Campos, Betzabé Irigoyen, Gonzalo Carrasco-Avino, Katiuska Bezares, Valentina Riquelme, Arnoldo Riquelme, Marco Arrese, Francisco Barrera
Abstract
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.
Conflict of interest statement
The authors declare no conflict of interest.
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