Published in:
21-10-2023 | Capsaicin | Original Article
Complementary role of peripheral and central autonomic nervous system on insulin-like growth factor-1 activation to prevent fatty liver disease
Published in: Hepatology International | Issue 1/2024
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Background
Insulin-like growth factor-1 (IGF-1) is involved in the pathology of non-alcoholic fatty liver disease (NAFLD) and ameliorates fatty infiltration in the liver. It is activated by growth hormone (GH); however, the role of GH–IGF-1 axis in NAFLD developmental phase has not been well identified. Therefore, in this study, we focused on the effect of IGF-1 in NAFLD pathology and GH excretion activation from the pituitary gland by peripheral autonomic neural pathways relaying liver–brain–gut pathway and by central neuropeptides.
Methods
GH and IGF-1 levels were assessed in wild-type and melanocortin-4 receptor knockout mice upon the development of diet-induced NAFLD. The contribution of the peripheral autonomic nervous system connecting the liver–brain–gut axis was assessed by its blockade using capsaicin and that of the central nervous system was assessed by the expression of hypothalamic brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRH), which activates GH release from the pituitary gland.
Results
In the NAFLD mouse models, the levels of GH and IGF-1 increased (p < .05). Further, hepatic fatty infiltration was suppressed even under peripheral autonomic nervous system blockade (p < .001), which inhibited gastric ghrelin expression. In mice with peripheral autonomic nervous blockade, hypothalamic BDNF and CRH were inhibited (p < .05), resulting in GH and IGF-1 excretion, whereas other neuropeptides of somatostatin and cortistatin showed no changes. These complementary effects were canceled in melanocortin-4 receptor knockout mice, which diminished BDNF and CRH release control.
Conclusions
Our study demonstrates that the release of IGF-1 by the nervous system is a key factor in maintaining the pathological homeostasis of NAFLD, suggesting its therapeutic potential.
Graphical Abstract
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