Mathies, Laura, Bettinger, Jill, Kumar, Naren, Crossen, Tyler, Wijesinghe, Dayanjan, Davies, Andrew, Contaifer, Daniel, Quamme, Elizabeth
[
International Worm Meeting,
2021]
The use of alcohol causes important physiological changes that contribute to the development of alcohol use disorder (AUD). These ethanol-induced changes are multifaceted and are incompletely characterized. In particular, the effects of ethanol on the composition and quantity of lipid species is under studied. We are particularly interested in lipidomic effects because several lines of evidence in our laboratory have implicated lipid metabolism in acute ethanol responses in worms. We therefore performed an unbiased lipidomic analysis of wild-type animals exposed for 16 hours to an intoxicating dose of ethanol. We found that several different lipid classes responded to the ethanol exposure, and that prominent among these was an increase in several different lipids containing odd-chain fatty acids (OCFA). C. elegans derive most OCFAs from their bacterial diet. In our ethanol exposure paradigm, the animals were exposed while feeding on OP50, so we examined if the bacteria were responding to the ethanol treatment. We found that the bacteria did not change their OCFA levels in response to ethanol, suggesting that the ethanol-induced increase in OCFA was due to effects on the worms themselves. We also observed that the long chain polyunsaturated omega-3 fatty acid eicosapentaenoic acid (EPA) appeared to be moved from its storage form in triacylglycerides to other phospholipid species, suggesting that it was mobilized in response to ethanol exposure. We have previously shown that EPA is required for normal acute behavioral responses to ethanol (Raabe et al., 2014), and that dietary EPA modulates ethanol response behaviors in mice (Wolstenholme et al., 2018). Both OCFA and EPA have been implicated in modulating membrane fluidity; this suggests a model in which animals modify their lipidomes in response to ethanol, perhaps to regulate the function of membrane proteins that are targets of ethanol. Together, these results lend new insight into the role of lipids in the response to ethanol exposure and provide a rich dataset for future studies.