{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:04:49Z","timestamp":1777478689480,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T00:00:00Z","timestamp":1545091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["MOP115021"],"award-info":[{"award-number":["MOP115021"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Obesity is associated with disrupted satiety regulation. Mice with diet\u2010induced obesity have reduced vagal afferent neuronal excitability and a decreased afferent response to satiety signals. A low grade inflammation occurs in obesity with increased expression of inducible nitric oxide synthase (iNOS).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of iNOS in diet\u2010induced obese mice restored vagal afferent neuronal excitability, increased the afferent response to satiety mediators and distention of the gut, and reduced short\u2010term energy intake.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A prolonged inhibition of iNOS reduced energy intake and body weight gain during the first week, and reduced amounts of epididymal fat after 3 weeks.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We identified a novel pathway underlying disrupted satiety regulation in obesity. Blocking of this pathway might be clinically useful for the management of obesity.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Vagal afferents regulate feeding by transmitting satiety signals to the brain. Mice with diet\u2010induced obesity have reduced vagal afferent sensitivity to satiety signals. We investigated whether inducible nitric oxide synthase (iNOS)\u2010derived NO contributed to this reduction. C57BL\/6J mice were fed a high\u2010 or low\u2010fat diet for 6\u20138 weeks. Nodose ganglia and jejunum were analysed by immunoblotting for iNOS expression; NO production was measured using a fluorometric assay. Nodose neuron excitability and intestinal afferent sensitivity were evaluated by whole\u2010cell patch clamp and <jats:italic>in vitro<\/jats:italic> afferent recording, respectively. Expression of iNOS and production of NO were increased in nodose ganglia and the small intestine in obese mice. Inhibition of iNOS in obese mice by pre\u2010treatment with an iNOS inhibitor increased nodose neuron excitability via 2\u2010pore\u2010domain K<jats:sup>+<\/jats:sup> channel leak currents, restored afferent sensitivity to satiety signals and reduced short\u2010term energy intake. Obese mice given the iNOS inhibitor daily for 3 weeks had reduced energy intake and decreased body weight gain during the first week, compared to mice given saline, and lower amounts of epididymal fat at the end of 3 weeks. Inhibition of iNOS or blocking the action of iNOS\u2010derived NO on vagal afferent pathways might comprise therapeutic strategies for hyperphagia and obesity.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp276894","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T01:04:44Z","timestamp":1545181484000},"page":"1487-1502","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Inducible nitric oxide synthase\u2010derived nitric oxide reduces vagal satiety signalling in obese mice"],"prefix":"10.1113","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8388-5825","authenticated-orcid":false,"given":"Yang","family":"Yu","sequence":"first","affiliation":[{"name":"Gastrointestinal Disease Research Unit Kingston General Hospital Queen's University  Kingston ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung 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