Stearoyl-CoA Desaturase 1 Is a Key Determinant of Membrane Lipid Composition in 3T3-L1 Adipocytes
| Autor: | Rachel M. Hagen, Sergio Rodriguez-Cuenca, Maria Fuller, Antonio Vidal-Puig, Lauren S. Whyte |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Physiology lcsh:Medicine Gene Expression Biochemistry chemistry.chemical_compound Mice Animal Cells Tandem Mass Spectrometry Lipid droplet Adipocytes Medicine and Health Sciences Homeostasis lcsh:Science Phospholipids Connective Tissue Cells Multidisciplinary Fatty Acids Cell Differentiation Lipids Cholesterol Connective Tissue lipids (amino acids peptides and proteins) Cellular Types Anatomy Sphingomyelin Stearoyl-CoA Desaturase Research Article Ceramide Spectrometry Mass Electrospray Ionization Membrane lipids Biology 03 medical and health sciences Membrane Lipids 3T3-L1 Cells Adipocyte Differentiation Genetics Animals Phosphatidylinositol Phosphatidylethanolamine lcsh:R Lipid microdomain Biology and Life Sciences Cell Biology 030104 developmental biology Biological Tissue chemistry lcsh:Q Stearoyl-CoA desaturase-1 Physiological Processes Developmental Biology Chromatography Liquid |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 9, p e0162047 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Stearoyl-CoA desaturase 1 (SCD1) is a lipogenic enzyme important for the regulation of membrane lipid homeostasis; dysregulation likely contributes to obesity associated metabolic disturbances. SCD1 catalyses the Δ9 desaturation of 12-19 carbon saturated fatty acids to monounsaturated fatty acids. To understand its influence in cellular lipid composition we investigated the effect of genetic ablation of SCD1 in 3T3-L1 adipocytes on membrane microdomain lipid composition at the species-specific level. Using liquid chromatography/electrospray ionisation-tandem mass spectrometry, we quantified 70 species of ceramide, mono-, di- and trihexosylceramide, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, bis(monoacylglycero)phosphate, phosphatidylinositol and cholesterol in 3T3-L1 adipocytes in which a 90% reduction in scd1 mRNA expression was achieved with siRNA. Cholesterol content was unchanged although decreases in other lipids resulted in cholesterol accounting for a higher proportion of lipid in the membranes. This was associated with decreased membrane lateral diffusion. An increased ratio of 24:0 to 24:1 in ceramide, mono- and dihexosylceramide, and sphingomyelin likely also contributed to this decrease in lateral diffusion. Of particular interest, we observed a decrease in phospholipids containing arachidonic acid. Given the high degree of structural flexibility of this acyl chain this will influence membrane lateral diffusion, and is likely responsible for the transcriptional activation of Lands' cycle enzymes lpcat3 and mboat7. Of relevance these profound changes in the lipidome were not accompanied by dramatic changes in gene expression in mature differentiated adipocytes, suggesting that adaptive homeostatic mechanisms to ensure partial maintenance of the biophysical properties of membranes likely occur at a post-transcriptional level. |
| Databáze: | OpenAIRE |
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