Using comprehensive lipid profiling to study effects of PFHxS during different stages of early zebrafish development

PFHxS (Perfluorohexane sulfonic acid) is one of the short-chain perfluoroalkyl substances (PFASs) which are widely used in many industrial and consumer applications. However, limited information is available on the molecular mechanism of PFHxS toxicity (e.g. lipid metabolism). This study provides in-depth information on the lipid regulation of zebrafish embryos with and without PFHxS exposure. Lipid changes throughout zebrafish development (4 to 120 h post fertilization (hpf)) were closely associated with lipid species and lipid composition (fatty acyl chains). A comprehensive lipid analysis of four different PFHxS exposures (0, 0.3, 1, 3, and 10 μM) at different zebrafish developmental stages (24, 48, 72, and 120 hpf) was performed. Data on exposure concentration, lipids, and developmental stage showed that all PFHxS concentrations dysregulated the lipid metabolism and these were developmental-dependent. The pattern of significantly changed lipids revealed that PFHxS caused effects related to oxidative stress, inflammation, and impaired fatty acid β-oxidation. Oxidative stress and inflammation caused the remodeling of glycerophospholipid (phosphatidylcholine (PC) and phosphatidylethanolamine (PE)), with increased incorporation of omega-3 PUFA and a decreased incorporation of omega-6 PUFA. [Display omitted] •Novel comprehensive overview on lipids in zebrafish embryos during 4and 120 hpf.•PFHxS strongly dysregulates lipid metabolism in developing zebrafish.•PFHxS remodels glycerophospholipid composition in zebrafish embryos.•Indication that PFHxS causes oxidative stress and inflammation in embryonic zebrafish.•Untargeted lipidomics is a promising tool to elucidate the mode of action of toxicants.