{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:36:53Z","timestamp":1785523013366,"version":"3.56.0"},"reference-count":76,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Macronutrients in the gastrointestinal (GI) lumen are able to activate \u201cintestinal brakes\u201d, feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) are regional differences (duodenum, jejunum, ileum) present in the intestinal luminal nutrient modulation of appetite and energy intake? (2) is this \u201cintestinal brake\u201d effect macronutrient specific? (3) is this \u201cintestinal brake\u201d effect maintained during repetitive activation? (4) can the \u201cintestinal brake\u201d effect be activated via non-caloric tastants? Recent evidence indicates that: (1) regional differences exist in the intestinal modulation of appetite and energy intake with a proximal to distal gradient for inhibition of energy intake: ileum and jejunum &gt; duodenum at low but not at high caloric infusion rates. (2) the \u201cintestinal brake\u201d effect on appetite and energy appears not to be macronutrient specific. At equi-caloric amounts, the inhibition on energy intake and appetite is in the same range for fat, protein and carbohydrate. (3) data on repetitive ileal brake activation are scarce because of the need for prolonged intestinal intubation. During repetitive activation of the ileal brake for up to 4 days, no adaptation was observed but overall the inhibitory effect on energy intake was small. (4) the concept of influencing energy intake by intra-intestinal delivery of non-caloric tastants is intriguing. Among tastants, the bitter compounds appear to be more effective in influencing energy intake. Energy intake decreases modestly after post-oral delivery of bitter tastants or a combination of tastants (bitter, sweet and umami). Intestinal brake activation provides an interesting concept for preventive and therapeutic approaches in weight management strategies.<\/jats:p>","DOI":"10.3390\/nu13051601","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T11:30:16Z","timestamp":1620732616000},"page":"1601","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Review on the Regional Effects of Gastrointestinal Luminal Stimulation on Appetite and Energy Intake: (Pre)clinical Observations"],"prefix":"10.3390","volume":"13","author":[{"given":"Jennifer","family":"Wilbrink","sequence":"first","affiliation":[{"name":"Division of Gastroenterology-Hepatology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwen","family":"Masclee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology-Hepatology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Klaassen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology-Hepatology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"van Avesaat","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology-Hepatology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-9980","authenticated-orcid":false,"given":"Daniel","family":"Keszthelyi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology-Hepatology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"},{"name":"NUTRIM School of Nutrition and Translational Research in Metabolism, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Masclee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology-Hepatology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands"},{"name":"NUTRIM School of Nutrition and Translational Research in Metabolism, 6229 ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1172\/JCI30227","article-title":"Gastrointestinal regulation of food intake","volume":"117","author":"Cummings","year":"2007","journal-title":"J. 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