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Our data demonstrate that injection of Botox into the proximal intestinal wall of diet-induced obese (DIO) mice induces weight loss and reduces food intake. This was associated with amelioration of hyperglycemia, hyperlipidemia, and significant improvement of glucose tolerance without alteration of energy expenditure. We also observed accelerated gastrointestinal transit and significant reductions in glucose and lipid absorption, which may account, at least in part, for the observed weight loss and robust metabolic benefits, although possible systemic effects occurring as a consequence of central and\/or peripheral signaling cannot be ignored. The observed metabolic benefits were found to be largely independent of weight loss, as demonstrated by pair-feeding experiments. Effects lasted \u223c8 weeks, for as long as the half-life of Botox as reported in prior rodent studies. These results have valuable clinical implications. If the observed effects are translatable in humans, this approach could lay the foundation for therapeutic approaches geared toward robust and sustained weight loss, mimicking some of the benefits of bariatric operations without its cost and complications.<\/jats:p>","DOI":"10.2337\/db21-0708","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T14:33:48Z","timestamp":1651070028000},"page":"1424-1438","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":4,"title":["Botulinum Injection Into the Proximal Intestinal Wall of Diet-Induced Obese Mice Leads to Weight Loss and Improves Glucose and Fat Tolerance"],"prefix":"10.2337","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-8413","authenticated-orcid":false,"given":"Sinju","family":"Sundaresan","sequence":"first","affiliation":[{"name":"1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN"},{"name":"2Department of Physiology, Midwestern University, Downers Grove, IL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Antoun","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Babak","family":"Banan","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamie","family":"Adcock","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connor","family":"Johnson","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan","family":"Claire","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kala","family":"Dixon","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce","family":"Flynn","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyndya A.","family":"Shibao","sequence":"additional","affiliation":[{"name":"2Department of Physiology, Midwestern University, Downers Grove, IL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naji","family":"Abumrad","sequence":"additional","affiliation":[{"name":"1Department of Surgery, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"2022062413522210800_B1","unstructured":"Hales CM , CarrollMD, FryarCD, OgdenCL. 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