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Research article - Peer-reviewed, 2021

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

Hana, Claudia A.; Tran, Lan, V; Moelzer, Christine; Muellner, Elisabeth; Hoermann-Wallner, Marlies; Franzke, Bernhard; Tosevska, Anela; Zoehrer, Patrick A.; Doberer, Daniel; Marculescu, Rodrig; Bulmer, Andrew C.; Freisling, Heinz; Moazzami, Ali A.; Wagner, Karl-Heinz


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.


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

Published in

2021, volume: 125, article number: 154913

Authors' information

Hana, Claudia A.
University of Vienna
Tran, Lan
University of Vienna
Moelzer, Christine
University of Aberdeen
Tosevska, Anela
University of Vienna
Müllner, Elisabeth
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Franzke, Bernhard
University of Vienna
Tosevska, Anela
Medical University of Vienna
Zoehrer, Patrick A.
University of Vienna
Doberer, Daniel
Medical University of Vienna
Marculescu, Rodrig
Medical University of Vienna
Bulmer, Andrew C.
Griffith University
Freisling, Heinz
International Agency for Research on Cancer (IARC)
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Wagner, Karl-Heinz
University of Vienna

Sustainable Development Goals

SDG3 Good health and wellbeing

UKÄ Subject classification

Endocrinology and Diabetes

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