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Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals

Hana, Claudia A. and Tran, Lan and Moelzer, Christine and Tosevska, Anela and Müllner, Elisabeth and Franzke, Bernhard and Tosevska, Anela and Zoehrer, Patrick A. and Doberer, Daniel and Marculescu, Rodrig and Bulmer, Andrew C. and Freisling, Heinz and Moazzami, Ali and Wagner, Karl-Heinz (2021). Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals. Metabolism. 125 , 154913
[Research article]

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Abstract

Background: The protective role of mildly elevated bilirubin against CVD and diabetes mellitus type 2 (DMT2) is associated with a favorable lipid phenotype. As the mechanistic understanding of this protection in humans remains elusive, we aimed to assess the metabolomics profile of mildly hyperbilirubinemic (Gilbert's syndrome; GS) individuals especially targeting lipid catabolism. Methods and results: Using NMR serum metabolomics of 56 GS individuals and 56 age and gender-matched healthy controls, GS individuals demonstrated significantly greater concentrations of acetylcarnitine (+20%, p < 0.001) and the ketone bodies, 3-hydroxybutyric acid (+132%, p < 0.001), acetoacetic acid (+95%, p < 0.001) and acetone (+46%, p < 0.001). Metabolites associated with an increased mitochondrial lipid metabolism such as citrate (+15%, p < 0.001), anaplerotic amino acid intermediates and creatinine were significantly greater and creatine significantly reduced in GS individuals. Stimulators of lipid catabolism including AMPK (+59%, p < 0.001), pPPAR alpha (+24%, p < 0.001) and T3 (+9%, p = 0.009) supported the metabolomics data while concomitantly blood glucose and insulin (-33%, p = 0.002) levels were significantly reduced. We further showed that the increased lipid catabolism partially mediates the favorable lipid phenotype (lower triglycerides) of GS individuals. Increased trimethylamine (+35%, p < 0.001) indicated changes in trimethylamine metabolism, an emerging predictor of metabolic health. Conclusion: We showed an enhanced lipid catabolism in mildly hyperbilirubinemic individuals, novel evidence as to why these individuals are leaner and protected against chronic metabolic diseases emphasizing bilirubin to be a promising future target in obese and dyslipidemia patients. (c) 2021 Published by Elsevier Inc.

Authors/Creators:Hana, Claudia A. and Tran, Lan and Moelzer, Christine and Tosevska, Anela and Müllner, Elisabeth and Franzke, Bernhard and Tosevska, Anela and Zoehrer, Patrick A. and Doberer, Daniel and Marculescu, Rodrig and Bulmer, Andrew C. and Freisling, Heinz and Moazzami, Ali and Wagner, Karl-Heinz
Title:Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals
Series Name/Journal:Metabolism
Year of publishing :2021
Volume:125
Article number:154913
Number of Pages:11
Publisher:W B SAUNDERS CO-ELSEVIER INC
ISSN:0026-0495
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 302 Clinical Medicine > Endocrinology and Diabetes
Keywords:Bilirubin, Metabolomics, Lipid catabolism, Ketone bodies, Gilbert's syndrome
URN:NBN:urn:nbn:se:slu:epsilon-p-114435
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-114435
Additional ID:
Type of IDID
DOI10.1016/j.metabol.2021.154913
Web of Science (WoS)000718923100003
ID Code:26212
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Molecular Sciences
Deposited By: SLUpub Connector
Deposited On:25 Nov 2021 14:25
Metadata Last Modified:25 Nov 2021 14:31

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