Knock-out of α-, β-, and γ-synuclein genes in mice leads to changes in the distribution of several lipids in the liver and blood plasma
Background: In addition to the role of synuclein proteins in synaptic transmission through binding with lipid membranes, the function of synucleins in reactions of the synthesis of lipids and fatty acids is also widely studied. Studying the disruption of lipid metabolism in Parkinson’s disease caused by synuclein dysfunction is particularly interesting. The aim of the study: To determine the effect of the absence of synuclein family proteins on the total lipid content and the ratio of different lipid classes in the liver and blood plasma in transgenic mice. Materials and methods: Measurement of lipid classes of αβγ-synuclein triple knockout mice (N=6) and wild type controls (N=6) was performed by the HPLC on the silica gel plates. Results: A 1.4-fold (P<0.05) increase in the percentage of total polar lipids was detected in the liver of knockout mice compared with the wild type, while the relative content of triglycerides decreased 1.2-fold (P<0.05), respectively. At the same time plasma levels of the polar lipids and triacylglycerols were unaltered. The lack of synucleins causes changes in the levels of fatty acids in comparison to wild type animals: C16:0 levels increased 1.2-fold in the liver (P<0.05) and 1.8-fold in plasma (P<0.05), and C18:1n9 levels increased both 1.4-fold (P<0.05) in plasma and 1.2-fold in the liver (P<0.05). C20:4n6 levels decreased 1.5-fold (P<0.05) in the liver of nonsynuclein mice. C18:2n6 levels decreased 7-fold in plasma (P<0.05), but did not change in liver. Conclusion: Our data demonstrate that the absence of all three members of the synuclein family causes disruption of lipid metabolism and leads to altered synthesis of fatty acids and hepatic lipid accumulation.
Lysikova EA, Chaprov KD. Knock-out of α-, β-, and γ-synuclein genes in mice leads to changes in the distribution of several lipids in the liver and blood plasma. Research Results in Biomedicine. 2022;8(4):448-456. Russian. DOI: 10.18413/2658-6533-2022-8-4-0-4
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