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

Molecules. 2017 Oct 13;22(10):1718. doi: 10.3390/molecules22101718.

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.

Keywords: C17:0; Hacl1; alpha-oxidation; biomarker; heptadecanoic acid; odd chain fatty acid; pentadecanoic acid; peroxisomes.

MeSH terms

  • Adipose Tissue / enzymology
  • Animals
  • Carbon-Carbon Lyases / genetics
  • Carbon-Carbon Lyases / physiology*
  • Enoyl-CoA Hydratase / genetics*
  • Fatty Acids / biosynthesis
  • Fatty Acids / genetics*
  • Humans
  • Liver / enzymology*
  • Mice
  • Mice, Knockout
  • Oxidation-Reduction
  • Peroxisomes / enzymology*
  • Peroxisomes / genetics
  • Tissue Distribution / genetics

Substances

  • Fatty Acids
  • Carbon-Carbon Lyases
  • HACL1 protein, human
  • Hacl1 protein, mouse
  • Enoyl-CoA Hydratase
  • margaric acid