{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:01:06Z","timestamp":1791558066683,"version":"4.3.4"},"reference-count":88,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007514","name":"Universit\u00e0 di Pisa","doi-asserted-by":"publisher","award":["PRA_2020_46"],"award-info":[{"award-number":["PRA_2020_46"]}],"id":[{"id":"10.13039\/501100007514","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Enteric neurogenic\/inflammation contributes to bowel dysmotility in obesity. We examined the role of NLRP3 in colonic neuromuscular dysfunctions in mice with high\u2010fat diet (HFD)\u2010induced obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Wild\u2010type C57BL\/6J and NLRP3\u2010KO (<jats:italic>Nlrp3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice were fed with HFD or standard diet for 8\u2009weeks. The activation of inflammasome pathways in colonic tissues from obese mice was assessed. The role of NLRP3 in in vivo colonic transit and in vitro tachykininergic contractions and substance P distribution was evaluated. The effect of substance P on NLRP3 signalling was tested in cultured cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>HFD mice displayed increased body and epididymal fat weight, cholesterol levels, plasma resistin levels and plasma and colonic IL\u20101\u03b2 levels, colonic inflammasome adaptor protein apoptosis\u2010associated speck\u2010like protein containing caspase\u2010recruitment domain (ASC) and caspase\u20101 mRNA expression and ASC immunopositivity in macrophages. Colonic tachykininergic contractions were enhanced in HFD mice. HFD NLRP3<jats:sup>\u2212\/\u2212<\/jats:sup> mice developed lower increase in body and epididymal fat weight, cholesterol levels, systemic and bowel inflammation. In HFD <jats:italic>Nlrp3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, the functional alterations of tachykinergic pathways and faecal output were normalized. In THP\u20101 cells, substance P promoted IL\u20101\u03b2 release. This effect was inhibited upon incubation with caspase\u20101 inhibitor or NK<jats:sub>1<\/jats:sub> antagonist and not observed in ASC<jats:sup>\u2212\/\u2212<\/jats:sup> cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>In obesity, NLRP3 regulates an interplay between the shaping of enteric immune\/inflammatory responses and the activation of substance P\/NK<jats:sub>1<\/jats:sub> pathways underlying the onset of colonic dysmotility. Identifying NLRP3 as a therapeutic target for the treatment of bowel symptoms related to obesity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15532","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T22:04:06Z","timestamp":1621289046000},"page":"3924-3942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["NLRP3 at the crossroads between immune\/inflammatory responses and enteric neuroplastic remodelling in a mouse model of diet\u2010induced obesity"],"prefix":"10.1111","volume":"178","author":[{"given":"Carolina","family":"Pellegrini","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Pisa  Pisa Italy"},{"name":"Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health University of Manchester, Manchester Academic Health Science Centre  Manchester 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