title: Age-Related Lipid Metabolic Signature in Human LMNA-Lipodystrophic Stem Cell-Derived Adipocytes.
abstract: BACKGROUND
  Lamin A (LMNA)-linked lipodystrophies belong to a group of clinical disorders characterized by a redistribution of adipose tissue with a variable range of metabolic complications. The leading cause of these disorders is the nonphysiological accumulation of the lamin A precursor, prelamin A. However, the molecular mechanisms by which prelamin A induces the pathology remain unclear.
  
  
  OBJECTIVE
  The aim of this study is to use an experimental LMNA-lipodystrophy model based on human mesenchymal stem cell (hMSC)-derived adipocytes that accumulate prelamin A to gain deeper insights into the mechanisms governing these diseases.
  
  
  METHODS
  Prelamin A-induced or -noninduced hMSC-derived adipocytes were obtained from healthy donors. The study was performed at the Biocruces Health Research Institute.
  
  
  METHODS
  Lipolytic activity was determined by the measurement of glycerol and free fatty acids. Ultrastructural analysis was performed by electron microscopy. Flow cytometry was used to assess mitochondrial membrane potential, and ultra-performance liquid chromatography coupled to mass spectrometry was used to explore lipid profiles.
  
  
  RESULTS
  Prelamin A accumulating hMSC-derived adipocytes revealed increased lipolysis, mitochondrial dysfunction, and endoplasmic reticulum stress. Accumulation of prelamin A induces an altered lipid profile characterized by reduced diacylglyceride content, a higher ratio of monounsaturated over polyunsaturated fatty acids, and decreased stearoyl-coenzyme A desaturase-1 activity. In contrast, the ratio of diacylglycerophosphatidylcholine over diacylglycerophosphatidylethanolamine and the activity of phosphatidylethanolamine-methyltransferase were increased.
  
  
  CONCLUSIONS
  Prelamin A accumulation causes mitochondrial dysfunction, endoplasmic reticulum stress, and altered lipid metabolism resembling a premature aging phenotype.
authors.affiliation: Stem Cells and Cell Therapy Laboratory (P.S., A.I., G.R.d.E., C.I.R.), BioCruces Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, 46980 Valencia, Spain; and Unidad Mixta de Esclerosis Múltiple y Neurorregeneración (J.A.F.-M., M.G.-V.), IIS Hospital La Fe, 46026 Valencia, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sánchez
authors.affiliation: Stem Cells and Cell Therapy Laboratory (P.S., A.I., G.R.d.E., C.I.R.), BioCruces Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, 46980 Valencia, Spain; and Unidad Mixta de Esclerosis Múltiple y Neurorregeneración (J.A.F.-M., M.G.-V.), IIS Hospital La Fe, 46026 Valencia, Spain.
authors.forename: Arantza
authors.initials: A
authors.lastname: Infante
authors.affiliation: Stem Cells and Cell Therapy Laboratory (P.S., A.I., G.R.d.E., C.I.R.), BioCruces Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, 46980 Valencia, Spain; and Unidad Mixta de Esclerosis Múltiple y Neurorregeneración (J.A.F.-M., M.G.-V.), IIS Hospital La Fe, 46026 Valencia, Spain.
authors.forename: Garbiñe Ruiz
authors.initials: GR
authors.lastname: de Eguino
authors.affiliation: Stem Cells and Cell Therapy Laboratory (P.S., A.I., G.R.d.E., C.I.R.), BioCruces Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, 46980 Valencia, Spain; and Unidad Mixta de Esclerosis Múltiple y Neurorregeneración (J.A.F.-M., M.G.-V.), IIS Hospital La Fe, 46026 Valencia, Spain.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Fuentes-Maestre
authors.affiliation: Stem Cells and Cell Therapy Laboratory (P.S., A.I., G.R.d.E., C.I.R.), BioCruces Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, 46980 Valencia, Spain; and Unidad Mixta de Esclerosis Múltiple y Neurorregeneración (J.A.F.-M., M.G.-V.), IIS Hospital La Fe, 46026 Valencia, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-Verdugo
authors.affiliation: Stem Cells and Cell Therapy Laboratory (P.S., A.I., G.R.d.E., C.I.R.), BioCruces Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain; Laboratorio de Neurobiología Comparada, Instituto Cavanilles, Universidad de Valencia, CIBERNED, 46980 Valencia, Spain; and Unidad Mixta de Esclerosis Múltiple y Neurorregeneración (J.A.F.-M., M.G.-V.), IIS Hospital La Fe, 46026 Valencia, Spain.
authors.forename: Clara I
authors.initials: CI
authors.lastname: Rodríguez
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000502:physiology; D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D034904:Lamin Type A / Q000235:genetics; D050356:Lipid Metabolism; D008060:Lipodystrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008066:Lipolysis; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D013234:Stem Cells / Q000473:pathology / Q000502:physiology; D055815:Young Adult
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A