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Hepatic Synaptotagmin 1 is involved in the remodelling of liver plasma- membrane lipid composition and gene expression in male Apoe-deficient mice consuming a Western diet

Publicado en:Biochimica Et Biophysica Acta-Molecular And Cell Biology Of Lipids. 1865 (12): - 2020-12-01 1865(12), doi: 10.1016/j.bbalip.2020.158790

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Resúmen: Background and aims. The molecular mechanisms by which the liver develops steatotic disease still remain unclear. Previous studies using nutritional and genetic models of hepatic steatosis in mice showed that liver synaptotagmin 1 (Syt1) expression was associated with lipid droplet area. Hepatic Syt1 overexpression was used as a tool to explore its effect on hepatic and plasma lipids. Methods and results: To find out a cause-effect, hepatic mouse Syt1 mRNA was cloned into a vector driving hepatocyte-specific expression and administered by hydrodynamic injection to male Apoe-deficient mice fed on a Western diet, the latter as a model of rapid spontaneous steatosis development. Hepatic microsomal, large vesicle, lysosomal and plasma membrane fractions were enriched in SYT1 protein following gene overexpression. In these conditions, very low density lipoprotein esterified cholesterol increased. Likewise, the transgene caused an alteration in lipid droplet surface and a positive correlation between Syt1 expression and hepatic total cholesterol content. A lipidomic approach evidenced a decrease in lysophosphatidylcholine, phosphatidylcholine and triglycerides in isolated plasma membrane fraction. Expressions of genes involved in biosynthesis of bile acids, fatty acid metabolism, lipoprotein dynamics and vesicular transport were modified by the increased SYT1 expression. Conclusions: These results indicate that this protein is involved in hepatic management of lipids and in the regulation of genes involved in lipid metabolism. © 2020 Elsevier B.V.

Palabras clave: Abc transporter subfamily a; Acetyl coenzyme a carboxylase; Acetyl coenzyme a carboxylase alpha; Acetyl coenzyme a carboxylase beta; Acyl coenzyme a desaturase 1; Adverse event; Animal; Animal cell; Animal tissue; Animals; Apoe-deficient mice; Apolipoprotein a2; Apolipoprotein e; Apolipoproteins e; Article; C57bl mouse; Carnitine palmitoyltransferase i; Carnitine palmitoyltransferase ia; Cell membrane; Cholestanetriol 26 monooxygenase; Cholesterol 7alpha monooxygenase; Cholesterol blood level; Cholesterol liver level; Cytochrome p450 7b1; Cytochrome p450 family 7; Diacylglycerol acyltransferase 1; Diacylglycerol acyltransferase 2; Diet, western; Fat droplet; Fatty liver; Gene deletion; Gene expression; Genetics; Hep g2 cells; Hepatic expression; Humans; Lipid; Lipid droplets; Lipid metabolism; Lipoprotein metabolism; Liver; Liver cell; Liver cell membrane; Liver homogenate; Liver microsome; Low density lipoprotein receptor; Lysophosphatidylcholine; Male; Messenger rna; Metabolism; Mice; Mice, inbred c57bl; Microsomal triglyceride transfer protein; Mouse; Multidrug resistance protein 1; Nonhuman; Open reading frame; Peroxisome proliferator activated receptor gamma coactivator 1alpha; Peroxisome proliferator activated receptor gamma coactivator 1beta; Phosphatidylcholine; Phosphatidylcholine sterol acyltransferase; Phosphatidylethanolamine; Plasma membrane lipids; Priority journal; Scavenger receptor bi; Synaptobrevin 2; Synaptotagmin 1; Synaptotagmin i; Syt1; Syt1 protein, mouse; Tissue distribution; Triacylglycerol; Unclassified drug; Very low density lipoprotein cholesterol; Western diet

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