Medium Chain Fatty Acids Cause Toxicity in C. Elegans

Bolduc, Juliet

Student Work

Medium Chain Fatty Acids Cause Toxicity in C. Elegans

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Fatty acids are the main component of cell membranes and are also involved in energy storage and signaling. This research sought to investigate the transcriptomic and metabolomic response to the supplementation of fatty acids in the free-living nematode Caenorhabditis elegans. To achieve this, four medium chain fatty acids were supplemented, with chain lengths ranging from six to ten carbons. These fatty acids have not been previously detected in C. elegans by analytical measurements like Gas Chromatography-Mass Spectrometry (GC-MS). Additionally, genetic machinery related to the modification and breakdown of medium chain fatty acids in C. elegans has yet to be fully annotated. Supplementation of these medium chain fatty acids caused toxicity in the animal. Gene expression profiling via RNA-sequencing showed fatty acids supplementation caused an upregulation of genes related to lipid metabolism and stress response. Specifically, the peroxisomal fatty acid degradation pathway was enriched, along with mitochondrial fatty acid degradation and steroid metabolism, but to a lesser degree. Additionally, the metabolomic data, obtained by GC-MS, indicated that the supplemented fatty acids are not detected in the animal, with the exception of the capric acid, a fatty acid with a chain length of 10 carbons. Even so, the detection of capric acid was very low as compared to other fatty acids present in the profile. Therefore, it can be concluded that medium chain fatty acids are toxic, but metabolizable by C. elegans. Given the gene expression analysis, it can be concluded that the supplemented fatty acids are likely being degraded in the peroxisome and the products are used in steroid metabolism pathways. This conclusion, along with the GC-MS data suggesting the supplemented fatty acids are not accumulating, leads to the conclusion that the toxicity observed is not related to accumulation of the fatty acid, and instead is likely occurring via another mechanism.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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