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Molecules 2017, 22(10), 1718; doi:10.3390/molecules22101718

Peroxisomal 2-Hydroxyacyl-CoA Lyase Is Involved in Endogenous Biosynthesis of Heptadecanoic Acid

1
NIHR BRC Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Pathology building Level 4, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
2
Medical Research Council Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
3
Laboratory of Lipid Biochemistry and Protein Interactions (LIPIT), Campus Gasthuisberg—KU Leuven, Herestraat Box 601, B-3000 Leuven, Belgium
*
Author to whom correspondence should be addressed.
Received: 30 August 2017 / Revised: 28 September 2017 / Accepted: 3 October 2017 / Published: 13 October 2017
(This article belongs to the Section Metabolites)
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Abstract

Circulating heptadecanoic acid (C17:0) is reported to be a pathology risk/prognosis biomarker and a dietary biomarker. This pathology relationship has been shown to be reliably predictive even when independent of dietary contributions, suggesting that the endogenous biosynthesis of C17:0 is related to the pathological aetiology. Little is known about C17:0 biosynthesis, which tissues contribute to the circulating levels, and how C17:0 is related to pathology. Hacl1+/− mice were mated to obtain Hacl1−/− and Hacl1+/+ control mice. At 14 weeks, they were anesthetized for tissue collection and fatty acid analysis. Compared to Hacl1+/+, C15:0 was not significantly affected in any Hacl1−/− tissues. However, the Hacl1−/− plasma and liver C17:0 levels were significantly lower: ~26% and ~22%, respectively. No significant differences were seen in the different adipose tissues. To conclude, Hacl1 plays a significant role in the liver and plasma levels of C17:0, providing evidence it can be endogenously biosynthesized via alpha-oxidation. The strong inverse association of C17:0 with pathology raises the question whether there is a direct link between α-oxidation and these diseases. Currently, there is no clear evidence, warranting further research into the role of α-oxidation in relation to metabolic diseases. View Full-Text
Keywords: Hacl1; alpha-oxidation; pentadecanoic acid; heptadecanoic acid; C17:0; biomarker; odd chain fatty acid; peroxisomes Hacl1; alpha-oxidation; pentadecanoic acid; heptadecanoic acid; C17:0; biomarker; odd chain fatty acid; peroxisomes
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Jenkins, B.; de Schryver, E.; Van Veldhoven, P.P.; Koulman, A. Peroxisomal 2-Hydroxyacyl-CoA Lyase Is Involved in Endogenous Biosynthesis of Heptadecanoic Acid. Molecules 2017, 22, 1718.

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