Seipin deficiency alters fatty acid Δ9 desaturation and lipid droplet formation in Berardinelli-Seip congenital lipodystrophy
| Autor: | Matthieu Prot, Sandra Grès, Yves Chrétien, Michèle Maurice, Jean-Sébastien Saulnier-Blache, Odile Colard, Jocelyne Magré, Mona Nemani, Haquima El Mourabit, Jacqueline Capeau, Anne-Marie Durand-Schneider, Emilie Boutet, Eliane Khallouf, Claude Wolf |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent BSCL2 Biology Biochemistry Seipin Young Adult chemistry.chemical_compound Lipodystrophy Congenital Generalized GTP-Binding Protein gamma Subunits Lipid droplet Internal medicine Lysophosphatidic acid medicine Humans Lymphocytes RNA Messenger Child Triglycerides Cell Line Transformed chemistry.chemical_classification Microscopy Confocal Reverse Transcriptase Polymerase Chain Reaction Infant Fatty acid Lipid metabolism General Medicine Phosphatidic acid 1-Acylglycerol-3-Phosphate O-Acyltransferase Lipid Metabolism medicine.disease Lipids Microscopy Electron Endocrinology chemistry Child Preschool Mutation Fatty Acids Unsaturated Female Lipodystrophy Stearoyl-CoA Desaturase |
| Zdroj: | Biochimie. 91:796-803 |
| ISSN: | 0300-9084 |
| DOI: | 10.1016/j.biochi.2009.01.011 |
| Popis: | Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare recessive disease characterized by near absence of adipose tissue and severe insulin resistance. In most cases, BSCL is due to loss-of-function mutations in the genes encoding either seipin of unknown function or 1-acyl-glycerol-3-phosphate O-acyltransferase 2 (AGPAT2) which catalyses the formation of phosphatidic acid from lysophosphatidic acid. We studied the lipid profile of lymphoblastoid cell-lines from 20 BSCL patients with null mutations in the genes encoding either seipin (n=12) or AGPAT2 (n=8) in comparison to nine control cell-lines. In seipin deficient cells, we observed alterations in the pattern of lipid droplets which were decreased in size and increased in number as compared to control cells. We also observed alterations in the triglycerides content as well as in the fatty acid composition from triglycerides and phosphatidylethanolamine, with an increased proportion of saturated fatty acids at the expense of the corresponding monounsaturated fatty acids, reflecting a defect in Delta9-desaturase activity. In AGPAT2 deficient cells, no specific alterations in lipid droplet pattern nor in fatty acid composition was observed but the cellular level of lysophosphatidic acid was increased as compared to that of control and seipin deficient cells. These results indicate that seipin like AGPAT2 is involved in lipid metabolism but exerts a different function. Seipin intervenes at a proximal step in triglycerides and phospholipids biosynthesis being involved in the pathway that links fatty acid Delta9 desaturation to lipid droplet formation. These findings provide new insights into how seipin deficiency causes severe lipodystrophy. |
| Databáze: | OpenAIRE |
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