{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:07:36Z","timestamp":1787756856636,"version":"build-2784847793"},"reference-count":51,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:p>Postprandial dyslipidemia is a metabolic condition commonly associated with insulin-resistant states, such as obesity and type 2 diabetes. It is characterized by the overproduction of intestinal chylomicron particles and excess atherogenic chylomicron remnants in circulation. We have previously shown that glucagon-like peptide 2 (GLP-2) augments dietary fat uptake and chylomicron production in insulin-resistant states; however, the underlying mechanisms remain unclear. Previous studies have implicated nitric oxide (NO) in the absorptive actions of GLP-2. In this study, we report a novel role for neuronal NO synthase (nNOS)\u2013mediated NO generation in lipid uptake and chylomicron formation based on studies in C57BL\/6J mice, nNOS\u2212\/\u2212 mice, and Syrian golden hamsters after intraduodenal and oral fat administration. GLP-2 treatment in wild-type (WT) mice significantly increased postprandial lipid accumulation and circulating apolipoprotein B48 protein levels, while these effects were abolished in nNOS\u2212\/\u2212 mice. nNOS inhibition in Syrian golden hamsters and protein kinase G (PKG) inhibition in WT mice also abrogated the effect of GLP-2 on postprandial lipid accumulation. These studies demonstrate a novel mechanism in which nNOS-generated NO is crucial for GLP-2\u2013mediated lipid absorption and chylomicron production in both mouse and hamster models. Overall, our data implicate an nNOS-PKG\u2013mediated pathway in GLP-2\u2013mediated stimulation of dietary fat absorption and intestinal chylomicron production.<\/jats:p>","DOI":"10.2337\/db21-1053","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T14:34:07Z","timestamp":1651070047000},"page":"1388-1399","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":17,"title":["GLP-2 Regulation of Dietary Fat Absorption and Intestinal Chylomicron Production via Neuronal Nitric Oxide Synthase (nNOS) Signaling"],"prefix":"10.2337","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9253-6520","authenticated-orcid":false,"given":"Elisabeth M.","family":"Grande","sequence":"first","affiliation":[{"name":"1Molecular Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"2Department of Physiology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fitore","family":"Raka","sequence":"additional","affiliation":[{"name":"1Molecular Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"2Department of Physiology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Hoffman","sequence":"additional","affiliation":[{"name":"1Molecular Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"3Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5839-5709","authenticated-orcid":false,"given":"Khosrow","family":"Adeli","sequence":"additional","affiliation":[{"name":"1Molecular Medicine, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"2Department of Physiology, University of Toronto, Toronto, Ontario, Canada"},{"name":"3Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"2022062413522048300_B1","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1053\/j.gastro.2007.03.052","article-title":"The epidemiology of obesity","volume":"132","author":"Ogden","year":"2007","journal-title":"Gastroenterology"},{"key":"2022062413522048300_B2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/BF02048544","article-title":"Elevated triglyceride-rich lipoproteins in diabetes. 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