{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:16:32Z","timestamp":1787498192068,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZonMW and Dutch Diabetes foundation","award":["95105011"],"award-info":[{"award-number":["95105011"]}]},{"name":"ZonMW and Dutch Diabetes foundation","award":["09150182010020"],"award-info":[{"award-number":["09150182010020"]}]},{"name":"ZONMW-VICI","award":["95105011"],"award-info":[{"award-number":["95105011"]}]},{"name":"ZONMW-VICI","award":["09150182010020"],"award-info":[{"award-number":["09150182010020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Cerebrotendinous xanthomatosis (CTX) is a rare inherited disease characterized by sterol 27-hydroxylase (CYP27A1) deficiency and, thus, a lack of bile acid synthesis with a marked accumulation of 7\u03b1-hydroxylated bile acid precursors. In addition to their renowned lipid-emulgating role, bile acids have been shown to stimulate secretion of the glucose-lowering and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1). In this paper, we examined postprandial bile acid, glucose, insulin, GLP-1 and fibroblast growth factor 19 (FGF19) plasma profiles in patients with CTX and matched healthy controls. Seven patients and seven age, gender and body mass index matched controls were included and subjected to a 4 h mixed meal test with regular blood sampling. CTX patients withdrew from chenodeoxycholic acid (CDCA) and statin therapy three weeks prior to the test. Postprandial levels of total bile acids were significantly lower in CTX patients and consisted of residual CDCA with low amounts of ursodeoxycholic acid (UDCA). The postprandial plasma glucose peak concentration occurred later in CTX patients compared to controls, and patients\u2019 insulin levels remained elevated for a longer time. Postprandial GLP-1 levels were slightly higher in CTX subjects whereas postprandial FGF19 levels were lower in CTX subjects. This novel characterization of CTX patients reveals very low circulating bile acid levels and FGF19 levels, aberrant postprandial glucose and insulin profiles, and elevated postprandial GLP-1 responses.<\/jats:p>","DOI":"10.3390\/nu15214625","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T12:48:31Z","timestamp":1698756511000},"page":"4625","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterization of Postprandial Bile Acid Profiles and Glucose Metabolism in Cerebrotendinous Xanthomatosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Soumia","family":"Majait","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Clinical Pharmacology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma C. E.","family":"Meessen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic Maxime","family":"Vaz","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Pediatrics, Amsterdam UMC Location University of Amsterdam, Laboratory Genetic Metabolic Diseases, Emma Children\u2019s Hospital, 1105 AZ Amsterdam, The Netherlands"},{"name":"Inborn Errors of Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism, 1105 AZ Amsterdam, The Netherlands"},{"name":"Core Facility Metabolomics, Amsterdam UMC location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Marleen","family":"Kemper","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine, Amsterdam University Medical Center, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel van","family":"Nierop","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Olde Damink","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1597-572X","authenticated-orcid":false,"given":"Frank G.","family":"Schaap","sequence":"additional","affiliation":[{"name":"Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, 6229 ER Maastricht, The Netherlands"},{"name":"Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes A.","family":"Romijn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Amsterdam UMC Location University of Amsterdam, 1012 WX Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Nieuwdorp","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aad","family":"Verrips","sequence":"additional","affiliation":[{"name":"Department of Neurology, Canisius Wilhelmina Hospital, 6532 SZ Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-5034","authenticated-orcid":false,"given":"Filip Krag","family":"Knop","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark"},{"name":"Steno Diabetes Center Copenhagen, 2730 Herlev, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1353 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten R.","family":"Soeters","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"ref_1","unstructured":"Clayton, P.T. (2022). Inborn Metabolic Diseases, Springer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbrc.2010.02.140","article-title":"Cerebrotendinous xanthomatosis: An inborn error in bile acid synthesis with defined mutations but still a challenge","volume":"396","author":"Hansson","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1152\/physrev.00010.2008","article-title":"Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation","volume":"89","author":"Lefebvre","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1080\/19490976.2015.1127483","article-title":"Consequences of bile salt biotransformations by intestinal bacteria","volume":"7","author":"Ridlon","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4S","DOI":"10.1002\/hep.1840040803","article-title":"Chemistry and enterohepatic circulation of bile acids","volume":"4","author":"Hofmann","year":"1984","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1210\/me.2008-0198","article-title":"Significance and mechanism of CYP7a1 gene regulation during the acute phase of liver regeneration","volume":"23","author":"Zhang","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1097\/01.MPG.0000150419.23031.2A","article-title":"Mutation in the sterol 27-hydroxylase gene associated with fatal cholestasis in infancy","volume":"40","author":"Alvelius","year":"2005","journal-title":"J. Pediatr. Gastr. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1001\/archneur.57.4.520","article-title":"Presence of diarrhea and absence of tendon xanthomas in patients with cerebrotendinous xanthomatosis","volume":"57","author":"Verrips","year":"2000","journal-title":"Arch. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1542\/peds.2008-0192","article-title":"Chronic diarrhea and juvenile cataracts: Think cerebrotendinous xanthomatosis and treat","volume":"123","author":"Berginer","year":"2009","journal-title":"Pediatrics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1049850","DOI":"10.3389\/fneur.2022.1049850","article-title":"Cerebrotendinous Xanthomatosis: A practice review of pathophysiology, diagnosis, and treatment","volume":"13","author":"Bernardes","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"937906","DOI":"10.3389\/fnins.2022.937906","article-title":"Gut microbiome-linked metabolites in the pathobiology of major depression with or without anxiety\u2014A role for bile acids","volume":"16","author":"MahmoudianDehkordi","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.clineuro.2013.12.008","article-title":"Long-term follow-up on the effect of combined therapy of bile acids and statins in the treatment of cerebrotendinous xanthomatosis: A case report","volume":"118","author":"Luyckx","year":"2014","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s13023-014-0179-4","article-title":"Cerebrotendinous xanthomatosis: A comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management","volume":"9","author":"Nie","year":"2014","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1007\/s11011-021-00714-7","article-title":"Patients with cerebrotendinous xanthomatosis diagnosed with diverse multisystem involvement","volume":"36","author":"Yildirim","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1126\/science.284.5418.1365","article-title":"Bile acids: Natural ligands for an orphan nuclear receptor","volume":"284","author":"Parks","year":"1999","journal-title":"Science"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1126\/science.284.5418.1362","article-title":"Identification of a nuclear receptor for bile acids","volume":"284","author":"Makishima","year":"1999","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S0006-291X(02)02550-0","article-title":"Identification of membrane-type receptor for bile acids (M-BAR)","volume":"298","author":"Maruyama","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nature04330","article-title":"Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation","volume":"439","author":"Watanabe","year":"2006","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cmet.2009.08.001","article-title":"TGR5-mediated bile acid sensing controls glucose homeostasis","volume":"10","author":"Thomas","year":"2009","journal-title":"Cell Metab."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Smits, M.M., and Holst, J.J. (2023). Endogenous glucagon-like peptide (GLP)-1 as alternative for GLP-1 receptor agonists: Could this work and how?. Diabetes\/Metab. Res. Rev., e3699.","DOI":"10.1002\/dmrr.3699"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1023\/A:1005543802724","article-title":"Rapid analysis of conjugated bile acids in plasma using electrospray tandem mass spectrometry: Application for selective screening of peroxisomal disorders","volume":"22","author":"Bootsma","year":"1999","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1002\/hep.22771","article-title":"High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis","volume":"49","author":"Schaap","year":"2009","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp","volume":"22","author":"Matsuda","year":"1999","journal-title":"Diabetes Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1093\/brain\/123.5.908","article-title":"Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis","volume":"123","author":"Verrips","year":"2000","journal-title":"Brain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.jacl.2018.06.008","article-title":"Diagnosis, treatment, and clinical outcomes in 43 cases with cerebrotendinous xanthomatosis","volume":"12","author":"Duell","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0306-9877(86)90137-4","article-title":"Bile acid-induced liver toxicity: Relation to the hydrophobic-hydrophilic balance of bile acids","volume":"19","author":"Attili","year":"1986","journal-title":"Med. Hypotheses"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1210\/jc.2016-1607","article-title":"Postprandial Plasma Concentrations of Individual Bile Acids and FGF-19 in Patients With Type 2 Diabetes","volume":"101","author":"Sonne","year":"2016","journal-title":"J. Clin. Endocr. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/oxfordjournals.jbchem.a022422","article-title":"Structure, evolution, and liver-specific expression of sterol 12\u03b1-hydroxylase P450 (CYP8B)","volume":"126","author":"Ishida","year":"1999","journal-title":"J. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1053\/j.gastro.2018.06.038","article-title":"An FXR agonist reduces bile acid synthesis independently of increases in FGF19 in healthy volunteers","volume":"155","author":"Rudling","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E494","DOI":"10.1152\/ajpendo.00534.2018","article-title":"Differential effects of a 40-hour fast and bile acid supplementation on human GLP-1 and FGF19 responses","volume":"317","author":"Meessen","year":"2019","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1021\/jm7015864","article-title":"Novel potent and selective bile acid derivatives as TGR5 agonists: Biological screening, structure\u2212activity relationships, and molecular modeling studies","volume":"51","author":"Sato","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.clnu.2017.06.015","article-title":"Transhepatic bile acid kinetics in pigs and humans","volume":"37","author":"Eggink","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s10545-017-0093-8","article-title":"Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX)","volume":"40","author":"Salen","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1111\/dom.12648","article-title":"Effect of chenodeoxycholic acid and the bile acid sequestrant colesevelam on glucagon-like peptide-1 secretion","volume":"18","author":"Hansen","year":"2016","journal-title":"Diabetes Obes. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/2193-1801-2-20","article-title":"Incretin secretion stimulated by ursodeoxycholic acid in healthy subjects","volume":"2","author":"Murakami","year":"2013","journal-title":"Springerplus"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1210\/jc.2016-1133","article-title":"Cholecystokinin-induced gallbladder emptying and metformin elicit additive glucagon-like peptide-1 responses","volume":"101","author":"Rohde","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/dom.13080","article-title":"The bile acid-sequestering resin sevelamer eliminates the acute GLP-1 stimulatory effect of endogenously released bile acids in patients with type 2 diabetes","volume":"20","author":"Rohde","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/cld.861","article-title":"Bile acid biology, pathophysiology, and therapeutics","volume":"15","author":"Chiang","year":"2020","journal-title":"Clin. Liver Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4829","DOI":"10.1172\/JCI68506","article-title":"Cholestenoic acids regulate motor neuron survival via liver X receptors","volume":"124","author":"Theofilopoulos","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1475-2891-8-22","article-title":"Indices of insulin sensitivity and secretion from a standard liquid meal test in subjects with type 2 diabetes, impaired or normal fasting glucose","volume":"8","author":"Maki","year":"2009","journal-title":"Nutr. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1089\/dia.2010.0083","article-title":"Repeatability of indices of insulin sensitivity and secretion from standard liquid meal tests in subjects with type 2 diabetes mellitus or normal or impaired fasting glucose","volume":"12","author":"Maki","year":"2010","journal-title":"Diabetes Technol. Ther."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/21\/4625\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:14:48Z","timestamp":1760130888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/21\/4625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":42,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["nu15214625"],"URL":"https:\/\/doi.org\/10.3390\/nu15214625","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]}}}