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Serum metabolomics ...
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Müllner, ElisabethSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för Molekylära vetenskaper,Department of Molecular Sciences
(författare)
Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals
- Artikel/kapitelEngelska2021
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Elsevier BV,2021
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WB Saunders,2024
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LIBRIS-ID:oai:slubar.slu.se:114435
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https://res.slu.se/id/publ/114435URI
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https://doi.org/10.1016/j.metabol.2021.154913DOI
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Språk:engelska
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Sammanfattning på:engelska
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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.
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Moazzami, AliSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för Molekylära vetenskaper,Department of Molecular Sciences(Swepub:slu)47697
(författare)
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Sveriges lantbruksuniversitetInstitutionen för Molekylära vetenskaper
(creator_code:org_t)
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Sveriges lantbruksuniversitet
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Ingår i:Metabolism: Elsevier BV1250026-04951532-8600
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