دورية أكاديمية
Glycodeoxycholic acid inhibits primary bile acid synthesis with minor effects on glucose- and lipid homeostasis in humans.
العنوان: | Glycodeoxycholic acid inhibits primary bile acid synthesis with minor effects on glucose- and lipid homeostasis in humans. |
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المؤلفون: | Meessen ECE; Department of Endocrinology and Metabolism, Amsterdam University Medical Centres - location AMC, University of Amsterdam, Amsterdam, The Netherlands., Majait S; Department of Pharmacy and Clinical Pharmacology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands., Ay Ü; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, The Netherlands.; Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Germany., Olde Damink SW; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, The Netherlands.; Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Germany., Romijn JA; Department of Internal Medicine, Amsterdam University Medical Centres - location AMC, University of Amsterdam, Amsterdam, The Netherlands., Holst JJ; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Hartmann B; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Kuipers F; Department of Paediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Nieuwdorp M; Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centres - location AMC, University of Amsterdam, Amsterdam, The Netherlands., Schaap FG; Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, The Netherlands.; Department of General, Visceral and Transplantation Surgery, RWTH University Hospital Aachen, Germany., Groen AK; Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centres - location AMC, University of Amsterdam, Amsterdam, The Netherlands., Kemper EM; Department of Pharmacy and Clinical Pharmacology, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.; Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centres - location AMC, University of Amsterdam, Amsterdam, The Netherlands., Soeters MR; Department of Endocrinology and Metabolism, Amsterdam University Medical Centres - location AMC, University of Amsterdam, Amsterdam, The Netherlands. |
المصدر: | The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2024 Jun 12. Date of Electronic Publication: 2024 Jun 12. |
Publication Model: | Ahead of Print |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375362 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-7197 (Electronic) Linking ISSN: 0021972X NLM ISO Abbreviation: J Clin Endocrinol Metab Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2017- : New York : Oxford University Press Original Publication: Springfield, Ill. : Charles C. Thomas |
مستخلص: | Background: Bile acids play vital roles in control of lipid-, glucose-, and energy metabolism by activating Takeda G protein-coupled receptor 5 (TGR5) and Farnesoid X receptor (FXR), the latter promoting production of the endocrine-acting fibroblast growth factor 19 (FGF19). Short-term administration of single bile acids has been reported to enhance plasma levels of GLP-1 and to enhance energy expenditure. However, prolonged bile acid supplementation, e.g. of chenodeoxycholic acid (CDCA) for gallstone dissolution, has been reported to have adverse effects. Study Design: In this proof-of-concept study, we assessed the safety and metabolic effects of oral glycine-conjugated deoxycholic acid (GDCA) administration at 10 mg/kg/day using regular and slow-release capsules (mimicking physiological bile acid release) over 30 days in two groups of each 10 healthy lean men respectively. Main Findings: GDCA increased postprandial total bile acid and FGF19 concentrations while suppressing those of the primary bile acids CDCA and cholic acid. Plasma levels of 7α-hydroxy-4-cholesten-3-one were reduced, indicating repressed hepatic bile acid synthesis. There were minimal effects on indices of lipid-, glucose-, and energy metabolism. No serious adverse events were reported during GDCA administration in either capsule types, although 50% of participants showed mild increases in plasma levels of liver transaminases and 80% (regular capsules) and 50% (slow-release capsules) of participants experienced gastrointestinal adverse events. Conclusion: GDCA administration leads to elevated FGF19 levels and effectively inhibits primary bile acid synthesis, supporting therapy compliance and its effectiveness. However, effects on lipid, glucose- and energy metabolism were minimal, indicating that expanding the pool of this relatively hydrophobic bile acid does not impact energy metabolism in healthy subjects. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.) |
فهرسة مساهمة: | Keywords: Bile acids; Farnesoid X receptor; Glucagon-like peptide 1; Takeda G protein-coupled receptor 5; glycodeoxycholic acid; humans; metabolic diseases |
تواريخ الأحداث: | Date Created: 20240612 Latest Revision: 20240612 |
رمز التحديث: | 20240612 |
DOI: | 10.1210/clinem/dgae399 |
PMID: | 38864544 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1945-7197 |
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DOI: | 10.1210/clinem/dgae399 |