title: Skipped BSCL2 Transcript in Celia's Encephalopathy (PELD): New Insights on Fatty Acids Involvement, Senescence and Adipogenesis.
abstract: OBJECTIVE
  PELD (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.
  
  
  METHODS
  Cellular 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.
  
  
  RESULTS
  the 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.
  
  
  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.
authors.affiliation: Thyroid and Metabolic Diseases Unit (U.E.T.eM.), Department of Medicine, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS)-IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Sofía
authors.identifier: http://orcid.org/0000-0003-3887-0573
authors.initials: S
authors.lastname: Sánchez-Iglesias
authors.affiliation: Thyroid and Metabolic Diseases Unit (U.E.T.eM.), Department of Medicine, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS)-IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Alexander
authors.initials: A
authors.lastname: Unruh-Pinheiro
authors.affiliation: Thyroid and Metabolic Diseases Unit (U.E.T.eM.), Department of Medicine, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS)-IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Guillín-Amarelle
authors.affiliation: Thyroid and Metabolic Diseases Unit (U.E.T.eM.), Department of Medicine, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS)-IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: González-Méndez
authors.affiliation: Thyroid and Metabolic Diseases Unit (U.E.T.eM.), Department of Medicine, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS)-IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ruiz-Riquelme
authors.affiliation: Thyroid and Metabolic Diseases Unit (U.E.T.eM.), Department of Medicine, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS)-IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Blanca Leticia
authors.initials: BL
authors.lastname: Rodríguez-Cañete
authors.affiliation: Thyroid and Metabolic Diseases Unit (U.E.T.eM.), Department of Medicine, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS)-IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rodríguez-García
authors.affiliation: Unit of Medical Genetics and Dysmorphology, Division of Pediatrics, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Encarnación
authors.initials: E
authors.lastname: Guillén-Navarro
authors.affiliation: Section of Neuropediatrics, Division of Pediatrics, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Domingo-Jiménez
authors.affiliation: Thyroid and Metabolic Diseases Unit (U.E.T.eM.), Department of Medicine, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS)-IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Araújo-Vilar
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000096:biosynthesis / Q000235:genetics; D020271:Heredodegenerative Disorders, Nervous System / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008060:Lipodystrophy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation
chemical_list: C432679:BSCL2 protein, human; D005231:Fatty Acids, Unsaturated; D044388:GTP-Binding Protein gamma Subunits