Autonomic nervous system network and liver regeneration

Abstract

To date, various signal transducers, cytokines, growth factors, and hormones have been reported to play an important role in homeostasis of various organs. Various cells and organs are involved in the hepatic regeneration process, which proceeds as a result of the coordination of many factors. While these factors are well known to be involved in the liver regeneration after the liver injury, however, as the details of such mechanisms have not been sufficiently elucidated, the practical applicability of hepatic regeneration based on the action of these and cytokines growth factors is still unclear. In terms of the involvement of the autonomic nervous system in hepatic regeneration, cell proliferation resulting from direct signal transduction to the liver has also been reported and recent studies focusing on the inter-organ communication via neural network opened a novel aspect of this field for therapeutic applicability. Therefore, the appropriate understanding of the relationship between autonomic neural network and liver regeneration through various organs including brain, afferent nerve, efferent nerve, etc. is essential. This mini-review explains the principle of neural system involved in the inter-organ communication and its contribution on the liver regeneration upon the liver injury reviewing recent progress in this field.

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver

“…Furthermore, we have reported the involvement of the gastric ghrelin activation that relayed the afferent autonomic neural signal from the stomach to the hypothalamus to release insulin-like growth factor-1 (IGF-1) from the liver to ameliorate its fatty change (Nagoya et al, 2020). According to previous reports and our findings, signal transmission of the autonomic nervous system from the liver is involved in various hepatic pathologies connecting various organs in the body (Inoue et al, 2018;Kamimura et al, 2018;Nagoya et al, 2020;Hurr et al, 2019). However, its role in NAFLD pathogenesis and progression remains elusive and has not been clarified in detail.…”

“…Serotonin is a monoamine neurotransmitter, 90% of which has been found in the gastrointestinal tract, synthesized from tryptophan, and secreted from chromaffin cells of the small intestine (Berger et al, 2009). Serotonin is also known to have numerous functions, such as smooth muscle contraction of blood vessels and bronchi, acceleration of peristaltic movement (Berger et al, 2009), respiratory rhythm (Cinelli et al, 2020), regulation of β cells in the pancreas (Berger et al, 2009;Li et al, 2000), liver regeneration (Inoue et al, 2018;Kamimura et al, 2018), liver fibrosis (Kyritsi et al, 2020), protection against intestinal ischemia (Tackett et al, 2019) and food-seeking behavior (He et al, 2020), and its reuptake inhibitors are used as an antidepressant in relation to gastrointestinal symptoms (Salisbury et al, 2020). In addition, serotonin is reportedly involved in the fibrosis of NAFLD (Atallah et al, 2018), the modification of lipid metabolisms (Namkung et al, 2018), the activation of signal from serotonin receptor on the hepatocytes (Choi et al, 2018), and the modulation of autophagy and Notch signal (Martin et al, 2020).…”

“…For example, the autonomic nervous activity contributes to the suppression of hyperglycemia during liver damage by regulating pancreas β cell activity (Imai et al, 2008), to the progression of cancers (Hayakawa et al, 2017;Kamiya et al, 2019), to liver regeneration upon severe liver damage (Izumi et al, 2018) and to inflammatory bowel diseases (Teratani et al, 2020). In addition, we recently demonstrated that the autonomic nervous system contributes to liver regeneration through signal transduction from the damaged liver to activate serotonin synthesis in the small intestine through the afferent sympathetic nerves and the brain (Inoue et al, 2018;Kamimura et al, 2018). Furthermore, we have reported the involvement of the gastric ghrelin activation that relayed the afferent autonomic neural signal from the stomach to the hypothalamus to release insulin-like growth factor-1 (IGF-1) from the liver to ameliorate its fatty change (Nagoya et al, 2020).…”

Ghrelin‐insulin‐like growth factor‐1 axis is activated via autonomic neural circuits in the non‐alcoholic fatty liver disease

“…The absence of increases of c‐fos‐positive neurons in the arcuate nucleus, IGF‐1 release, and hypothalamic ghrelin in the PH group are also consistent with this hypothesis (Figures and ). Notably, the neural signal transduction from the steatosis changes in the liver with PH is not related to the appetite activated by the cerebral hormones and leads the signal to the small intestine to increase the level of serotonin . This may also be related to the reduction of intrahepatic nerve components after the hepatic resection.…”

Cell Sources and Influencing Factors of Liver Regeneration: A Review

“…Previous studies have discovered that there is a direct feedback relationship between the liver and the brain via the autonomic nervous system [ 101 ]. Izumi et al discovered that LR slowed down when the hepatic branches of the vagus nerve were resected in PH rat models [ 102 ].…”