title: Reduced UCP-1 content in in vitro differentiated beige/brite adipocytes derived from preadipocytes of human subcutaneous white adipose tissues in obesity.
abstract: BACKGROUND
  Brown adipose tissue (BAT) is a potential therapeutic target to reverse obesity. The purpose of this study was to determine whether primary precursor cells isolated from human adult subcutaneous white adipose tissue (WAT) can be induced to differentiate in-vitro into adipocytes that express key markers of brown or beige adipose, and whether the expression level of such markers differs between lean and obese young adult males.
  
  
  METHODS
  Adipogenic precursor cells were isolated from lean and obese individuals from subcutaneous abdominal WAT biopsies. Cells were grown to confluence, differentiated for 2.5 weeks then harvested for measurement of gene expression and UCP1 protein.
  
  
  RESULTS
  There was no difference between groups with respect to differentiation into adipocytes, as indicated by oil red-O staining, rates of lipolysis, and expression of adipogenic genes (FABP4, PPARG). WAT genes (HOXC9, RB1) were expressed equally in the two groups. Post differentiation, the beige adipose specific genes CITED1 and CD137 were significantly increased in both groups, but classic BAT markers ZIC1 and LHX8 decreased significantly. Cell lines from both groups also equally increased post-differentiation expression of the thermogenic-responsive gene PPARGC1A (PGC-1α). UCP1 gene expression was undetectable prior to differentiation, however after differentiation both gene expression and protein content were increased in both groups and were significantly greater in cultures from lean compared with obese individuals (p<0.05).
  
  
  CONCLUSIONS
  Human subcutaneous WAT cells can be induced to attain BAT characteristics, but this capacity is reduced in WAT cells from obese individuals.
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Carey
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Camilla
authors.initials: C
authors.lastname: Vorlander
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Medini
authors.initials: M
authors.lastname: Reddy-Luthmoodoo
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Alaina K
authors.initials: AK
authors.lastname: Natoli
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Melissa F
authors.initials: MF
authors.lastname: Formosa
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Bertovic
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Anderson
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Cardiology, The Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Duffy
authors.affiliation: Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Cardiology, The Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: Kingwell
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism* / Q000473:pathology; D052438:Adipocytes, White / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D061251:Primary Cell Culture; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; C512688:CITED1 protein, human; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D018398:Homeodomain Proteins; C522807:Hoxc9 protein, human; D007473:Ion Channels; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; C492123:ZIC1 protein, human