Triple-knockout, synuclein-free mice display compromised lipid pattern
Abstract Background: Recent studies have implicated synucleins in several reactions during the biosynthesis of lipids and fatty acids in addition to their recognised role in membrane lipid binding and synaptic functions. All members of the synuclein family interact robustly with lipid membranes, and appear to be important for the physiological functions of proteins while influencing the pathological aggregation of α-synuclein. Methods: The following tissues were used for lipid and fatty acid analysis: plasma, liver and two brain areas (cortex and midbrain). Lipid classes were separated using thin-layer chromatography. Fatty acids were analysed using gas chromatography. Results: We describe the importance of long-chain polyunsaturated fatty acids (LCPUFA) and palmitic acid in liver and plasma, reduced triacylglycerol (TAG) accumulation in liver and circulated plasma non-esterified fatty acids in synuclein free mice. In midbrain, observed changes in the relative concentrations of phosphatidylcholine (PC) and cerebrosides (CER) were counterbalanced. In midbrain, we recorded a notable reduction in ethanolamine plasmalogens in synuclein free mice and consider this an important finding considering the abnormal ether lipid metabolism usually associated with neurological disorders.Conclusions: In summary, our data demonstrate that synuclein deficiency can result in alterations of PUFA synthesis, storage lipid accumulation in liver, and reduction of plasmalogens and CER, those polar lipids which are principal compounds of lipid rafts in many tissues. An ablation of all three synuclein family members resulted in more pronounced lipid modifications then previously showed by us γ-synuclein deficiency. Possible mechanisms by which synuclein deficiency may govern the reported modifications of lipid metabolism in TKO mice are proposed and discussed.