{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:57:02Z","timestamp":1787590622568,"version":"build-2736575974"},"reference-count":11,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leona M. and Harry B. Helmsley Charitable Trust"},{"name":"Aase og Ejnar Danielsens Fond"},{"name":"A.P. M\u00f8ller Foundation"},{"name":"Jacob og Olga Madsens Fond"},{"name":"Novo Nordisk Foundation"},{"name":"Sanofi Aventis (Frankfurt, Germany)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objective: Cholesin is a recently discovered gut-derived hormone secreted by enterocytes upon dietary cholesterol uptake via the transmembrane sterol transporter Niemann\u2013Pick disease C1-like intracellular cholesterol transporter 1 (NPC1L1). In the liver, cholesin activates G protein-coupled receptor 146 (GPR146), causing reduced cholesterol synthesis. In this exploratory, hypothesis-generating study based on post hoc analysis, human data on the cholesin system are presented. Methods: Mucosal biopsies were collected throughout the intestinal tract from 12 individuals with type 2 diabetes (T2D) and 12 healthy, matched controls. Upper small intestinal mucosal biopsies were collected from 20 individuals before and after Roux-en-Y gastric bypass (RYGB) surgery. Liver biopsies were collected from 12 men with obesity and 15 matched controls without obesity. Subcutaneous abdominal adipose tissue biopsies were collected from 20 men with type 1 diabetes (T1D). All biopsies underwent full mRNA sequencing. Results: Cholesin mRNA expression was observed throughout the intestinal tracts of the individuals with T2D and the controls, in the livers of men with and without obesity, and in adipose tissue of men with T1D. NPC1L1 mRNA expression was robust throughout the small intestines but negligible in the large intestines of both individuals with and without T2D. RYGB surgery induced the expression of NPC1L1 mRNA in the upper small intestine. GPR146 mRNA was expressed in the livers of men, both with and without obesity, and in the adipose tissue of men with T1D, but not in the intestines. Conclusions: Our results suggest a role of the cholesin system in human physiology, but whether it is perturbed in metabolic diseases remains unknown. Clinical trial registration numbers: NCT03044860, NCT03093298, NCT02337660, NCT03734718.<\/jats:p>","DOI":"10.3390\/nu17040619","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T08:05:42Z","timestamp":1739347542000},"page":"619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cholesin mRNA Expression in Human Intestinal, Liver, and Adipose Tissues"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6999-1872","authenticated-orcid":false,"given":"Hannah","family":"Gilliam-Vigh","sequence":"first","affiliation":[{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital\u2014Herlev and Gentofte, DK-2900 Hellerup, Denmark"},{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte P.","family":"Suppli","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital\u2014Herlev and Gentofte, DK-2900 Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1582-1453","authenticated-orcid":false,"given":"Sebastian M. N.","family":"Heimb\u00fcrger","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital\u2014Herlev and Gentofte, DK-2900 Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asger B.","family":"Lund","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital\u2014Herlev and Gentofte, DK-2900 Hellerup, Denmark"},{"name":"Clinical Research, Steno Diabetes Center Copenhagen, DK-2730 Herlev, Denmark"},{"name":"Department of Clinical Medicine, The Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-5034","authenticated-orcid":false,"given":"Filip K.","family":"Knop","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital\u2014Herlev and Gentofte, DK-2900 Hellerup, Denmark"},{"name":"Department of Clinical Medicine, The Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-3908","authenticated-orcid":false,"given":"Anne-Marie","family":"Ellegaard","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Copenhagen University Hospital\u2014Herlev and Gentofte, DK-2900 Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/s41580-019-0190-7","article-title":"Mechanisms and regulation of cholesterol homeostasis","volume":"21","author":"Luo","year":"2020","journal-title":"Nat. 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