Abstract
ObjectivePELD (Progressive Encephalopathy with or without Lipodystrophy or Celia’s Encephalopathy) is a fatal and rare neurodegenerative syndrome associated with the BSCL2 mutation c.985C>T, that results in an aberrant transcript without the exon 7 (Celia seipin). The aim of this study was to evaluate both the process of cellular senescence and the effect of unsaturated fatty acids on preadipocytes from a homozygous c.985C>T patient. Also, the role of aberrant seipin isoform on adipogenesis was studied in adipose-derived human mesenchymal stem cells.Material and methodsCellular senescence was evaluated using β-galactosidase staining of preadipocytes obtained from a homozygous c.985C>T patient. Moreover, these cells were cultured during 24 hours with Intralipid, a soybean oil-based commercial lipid emulsion. The expression of the different BSCL2 transcripts was measured by qPCR. Adipose-derived human mesenchymal stem cells were differentiated to a fat lineage using StemPRO adipogenesis kit, and the expression of BSCL2 transcripts and several adipogenesis-related genes was measured by qPCR.Resultsthe treatment of preadipocytes with unsaturated fatty acids significantly reduced the expression of the BSCL2 transcript without exon 7 by 34 to 63%. On the other hand, at least in preadipocytes, this mutation does not disturb cellular senescence rate. Finally, during adipocyte differentiation of adipose-derived human mesenchymal stem cells, the expression of adipogenic genes (PPARG, LPIN1, and LPL) increased significantly over 14 days, and noteworthy is that the BSCL2 transcript without exon 7 was differentially expressed by 332 to 723% when compared to day 0, suggesting an underlying role in adipogenesis.Conclusionsour results suggest that Celia seipin is probably playing an underestimated role in adipocyte maturation, but not in senescence, and its expression can be modified by exogenous factors as fatty acids.
Highlights
Seipin is a protein whose function has not been yet fully elucidated
Adipose-derived human mesenchymal stem cells were differentiated to a fat lineage using StemPRO adipogenesis kit, and the expression of BSCL2 transcripts and several adipogenesis-related genes was measured by qPCR
Conclusions our results suggest that Celia seipin is probably playing an underestimated role in adipocyte maturation, but not in senescence, and its expression can be modified by exogenous factors as fatty acids
Summary
Seipin is a protein whose function has not been yet fully elucidated. Seipin is a membrane protein of the endoplasmic reticulum (ER). BSCL2 gene encodes mainly three transcripts of 462 (BSCL2-003, ENST00000360796; CCDS44627), 398 (BSCL2-004/005/006, ENST00000421906; ENST00000407022; ENST00000403550; CCDS8031) and 287 (BSCL2-008, ENST00000278893; CCDS55769) amino acids respectively. The first transcript described [1] was BSCL2-004/005/006. BSCL2-003 is identical to the first one except for a N-terminal extension of 64 amino acids encoded by exon 1. The 287-amino acid short transcript features skipping of exon 7, which results in a change in the reading frame, so that the resulting protein is completely different from the other two ones in the amino acid stretch encoded from exon 6 to exon 10
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