{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:01:24Z","timestamp":1782964884101,"version":"3.54.5"},"reference-count":57,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Utrecht University and Danone Nutricia Research &amp; Innovation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>During esophagectomy, the vagus nerve is transected, which may add to the development of postoperative complications. The vagus nerve has been shown to attenuate inflammation and can be activated by a high-fat nutrition via the release of acetylcholine. This binds to \u03b17 nicotinic acetylcholine receptors (\u03b17nAChR) and inhibits \u03b17nAChR-expressing inflammatory cells. This study investigates the role of the vagus nerve and the effect of high-fat nutrition on lipopolysaccharide (LPS)-induced lung injury in rats. Firstly, 48 rats were randomized in 4 groups as follows: sham (sparing vagus nerve), abdominal (selective) vagotomy, cervical vagotomy and cervical vagotomy with an \u03b17nAChR-agonist. Secondly, 24 rats were randomized in 3 groups as follows: sham, sham with an \u03b17nAChR-antagonist and cervical vagotomy with an \u03b17nAChR-antagonist. Finally, 24 rats were randomized in 3 groups as follows: fasting, high-fat nutrition before sham and high-fat nutrition before selective vagotomy. Abdominal (selective) vagotomy did not impact histopathological lung injury (LIS) compared with the control (sham) group (p &gt; 0.999). There was a trend in aggravation of LIS after cervical vagotomy (p = 0.051), even after an \u03b17nAChR-agonist (p = 0.090). Cervical vagotomy with an \u03b17nAChR-antagonist aggravated lung injury (p = 0.004). Furthermore, cervical vagotomy increased macrophages in bronchoalveolar lavage (BAL) fluid and negatively impacted pulmonary function. Other inflammatory cells, TNF-\u03b1 and IL-6, in the BALF and serum were unaffected. High-fat nutrition reduced LIS after sham (p = 0.012) and selective vagotomy (p = 0.002) compared to fasting. vagotomy. This study underlines the role of the vagus nerve in lung injury and shows that vagus nerve stimulation using high-fat nutrition is effective in reducing lung injury, even after selective vagotomy.<\/jats:p>","DOI":"10.3390\/nu15102327","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T01:52:41Z","timestamp":1684288361000},"page":"2327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the Modulatory Effect of High-Fat Nutrition on Lipopolysaccharide-Induced Acute Lung Injury in Vagotomized Rats and the Role of the Vagus Nerve"],"prefix":"10.3390","volume":"15","author":[{"given":"Maarten F. J.","family":"Seesing","sequence":"first","affiliation":[{"name":"Department of Surgery, University Medical Center Utrecht, Utrecht University, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7684-2624","authenticated-orcid":false,"given":"Henricus J. B.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Catharina Hospital, 5623 Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa C. M.","family":"Geraedts","sequence":"additional","affiliation":[{"name":"Department of Surgery, Catharina Hospital, 5623 Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teus J.","family":"Weijs","sequence":"additional","affiliation":[{"name":"Department of Surgery, Catharina Hospital, 5623 Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"van Ark","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4986-5497","authenticated-orcid":false,"given":"Thea","family":"Leusink-Muis","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-2192","authenticated-orcid":false,"given":"Gert","family":"Folkerts","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-9182","authenticated-orcid":false,"given":"Johan","family":"Garssen","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 Utrecht, The Netherlands"},{"name":"Danone Nutricia Research & Innovation, Immunology, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6584-1677","authenticated-orcid":false,"given":"Jelle P.","family":"Ruurda","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Medical Center Utrecht, Utrecht University, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grard A. P.","family":"Nieuwenhuijzen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Catharina Hospital, 5623 Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"van Hillegersberg","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Medical Center Utrecht, Utrecht University, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9483-1520","authenticated-orcid":false,"given":"Misha D. P.","family":"Luyer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Catharina Hospital, 5623 Eindhoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/ni1229","article-title":"Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway","volume":"6","author":"The","year":"2005","journal-title":"Nat. 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