{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T10:22:07Z","timestamp":1772878927905,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T00:00:00Z","timestamp":1580083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K19537"],"award-info":[{"award-number":["18K19537"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The correlation of the growth hormone (GH) and insulin\u2010like growth factor\u20101 (IGF\u20101) with non\u2010alcoholic fatty liver disease (NAFLD) has been reported in epidemiological studies. However, the mechanisms of molecular and inter\u2010organ systems that render these factors to influence on NAFLD have not been elucidated. In this study, we examined the induction of ghrelin which is the GH\u2010releasing hormone and IGF\u20101, and involvement of autonomic neural circuits, in the pathogenesis of NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The expression of gastric and hypothalamic ghrelin, neural activation in the brain, and serum IGF\u20101 were examined in NAFLD models of choline\u2010deficient defined l\u2010amino\u2010acid diet\u2010fed, melanocortin 4 receptor knockout mice, and partial hepatectomy mice with or without the blockades of autonomic nerves to test the contribution of neural circuits connecting the brain, liver, and stomach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The fatty changes in the liver increased the expression of gastric ghrelin through the autonomic pathways which sends the neural signals to the arcuate nucleus in the hypothalamus through the afferent vagal nerve which reached the pituitary gland to release GH and then stimulate the IGF\u20101 release from the liver. In addition, high levels of ghrelin expression in the arcuate nucleus were correlated with NAFLD progression regardless of the circuits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that the fatty liver stimulates the autonomic nervous signal circuits which suppress the progression of the disease by activating the gastric ghrelin expression, the neural signal transduction in the brain, and the release of IGF\u20101 from the liver.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13799","type":"journal-article","created":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T08:19:52Z","timestamp":1580113192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ghrelin\u2010insulin\u2010like growth factor\u20101 axis is activated via autonomic neural circuits in the non\u2010alcoholic fatty liver disease"],"prefix":"10.1111","volume":"32","author":[{"given":"Takuro","family":"Nagoya","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7182-4400","authenticated-orcid":false,"given":"Kenya","family":"Kamimura","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Niigata Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryosuke","family":"Inoue","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University Niigata 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