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Hana CA, Tran LV, Mölzer C, et al. Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals. Metabolism. 2021;125:154913doi: 10.1016/j.metabol.2021.154913.
Hana, C. A., Tran, L. V., Mölzer, C., Müllner, E., Hörmann-Wallner, M., Franzke, B., Tosevska, A., Zöhrer, P. A., Doberer, D., Marculescu, R., Bulmer, A. C., Freisling, H., Moazzami, A. A., & Wagner, K. H. (2021). Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals. Metabolism: clinical and experimental, 125154913. https://doi.org/10.1016/j.metabol.2021.154913
Hana, Claudia A, et al. "Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals." Metabolism: clinical and experimental vol. 125 (2021): 154913. doi: https://doi.org/10.1016/j.metabol.2021.154913
Hana CA, Tran LV, Mölzer C, Müllner E, Hörmann-Wallner M, Franzke B, Tosevska A, Zöhrer PA, Doberer D, Marculescu R, Bulmer AC, Freisling H, Moazzami AA, Wagner KH. Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals. Metabolism. 2021 Dec;125:154913. doi: 10.1016/j.metabol.2021.154913. Epub 2021 Oct 20. PMID: 34653509.
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Metabolism. 2021 Dec;125:154913. doi: 10.1016/j.metabol.2021.154913. Epub 2021 Oct 20.

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

Metabolism: clinical and experimental

Claudia A Hana, Lan V Tran, Christine Mölzer, Elisabeth Müllner, Marlies Hörmann-Wallner, Bernhard Franzke, Anela Tosevska, Patrick A Zöhrer, Daniel Doberer, Rodrig Marculescu, Andrew C Bulmer, Heinz Freisling, Ali A Moazzami, Karl-Heinz Wagner

Affiliations

  1. Faculty of Lifesciences, Department of Nutritional Sciences, University of Vienna, Vienna, Austria. Electronic address: [email protected].
  2. Faculty of Lifesciences, Department of Nutritional Sciences, University of Vienna, Vienna, Austria.
  3. School of Medicine, Institute of Medical Sciences, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
  4. Department of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
  5. Institute for Dietetics and Nutrition, University of Applied Sciences FH JOANNEUM, Graz, Austria.
  6. Faculty of Lifesciences, Department of Nutritional Sciences, University of Vienna, Vienna, Austria; Research Platform Active Ageing, University of Vienna, Vienna, Austria.
  7. Faculty of Lifesciences, Department of Nutritional Sciences, University of Vienna, Vienna, Austria; Internal Medicine III, Division of Rheumatology, Medical University of Vienna; Vienna, Austria.
  8. Department of Clinical Pharmacology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
  9. Clinical Institute of Laboratory Medicine, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
  10. School of Medical Science and Menzies Health Institute Queensland, Griffith University, Queensland, Australia.
  11. Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO), Lyon, France.
  12. Faculty of Lifesciences, Department of Nutritional Sciences, University of Vienna, Vienna, Austria; Research Platform Active Ageing, University of Vienna, Vienna, Austria. Electronic address: [email protected].

PMID: 34653509 DOI: 10.1016/j.metabol.2021.154913

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), pPPARα (+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.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: Bilirubin; Gilbert's syndrome; Ketone bodies; Lipid catabolism; Metabolomics

Conflict of interest statement

Declaration of competing interest None, the authors have declared that no conflict of interest exists.

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