title: Expression of adipogenic transcription factors, peroxisome proliferator-activated receptor gamma co-activator 1, IL-6 and CD45 in subcutaneous adipose tissue in lipodystrophy associated with highly active antiretroviral therapy.
abstract: OBJECTIVE
  To determine the expressions of multiple genes in the subcutaneous adipose tissue of HIV-positive, highly active antiretroviral therapy (HAART)-treated patients with and without lipodystrophy.
  
  
  METHODS
  Real-time polymerase chain reaction was used to measure gene expressions in this cross-sectional study.
  
  
  RESULTS
  The messenger RNA concentrations of adipose transcription factors (peroxisome proliferator-activated receptor (PPAR) gamma and delta and sterol regulatory element binding protein 1c) were all significantly lower in the lipodystrophic than the non-lipodystrophic group. The mRNA concentration of PPAR-gamma co-activator 1 (PGC-1), which regulates mitochondrial biogenesis, was lower in the lipodystrophic than the non-lipodystrophic group. The mRNA expression of lipoprotein lipase, acyl coenzyme A synthase and glucose transport protein 4 were significantly lower in the lipodystrophic than the non-lipodystrophic group, but the mRNA concentrations of fatty acid transport and binding proteins were similar in both groups. The mRNA concentrations of IL-6 and CD45 (a common leukocyte marker) were significantly higher in the lipodystrophic than the non-lipodystrophic group.
  
  
  CONCLUSIONS
  Multiple alterations characterize gene expression in the subcutaneous adipose tissue of patients with HAART-associated lipodystrophy compared with HIV-positive, HAART-treated patients without lipodystrophy. The low expression of transcription factors inhibits adipocyte differentiation. The low expression of PGC-1 may contribute to mitochondrial defects. In addition, IL-6 and CD45 expressions are increased, the latter implying an excessive number of cells of leukocyte origin in lipodystrophic adipose tissue. Mitochondrial injury and an excess of proinflammatory cytokines may lead to increased apoptosis. All these changes may contribute to the loss of subcutaneous fat in HAART-associated lipodystrophy.
authors.affiliation: Department of Medicine, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Katja
authors.initials: K
authors.lastname: Kannisto
authors.forename: Jussi
authors.initials: J
authors.lastname: Sutinen
authors.forename: Elena
authors.initials: E
authors.lastname: Korsheninnikova
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Fisher
authors.forename: Ewa
authors.initials: E
authors.lastname: Ehrenborg
authors.forename: Karl
authors.initials: K
authors.lastname: Gertow
authors.forename: Antti
authors.initials: A
authors.lastname: Virkamäki
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Nyman
authors.forename: Hubert
authors.initials: H
authors.lastname: Vidal
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000199:Actins / Q000235:genetics; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D003066:Coenzyme A Ligases / Q000235:genetics; D003430:Cross-Sectional Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D050612:Fatty Acid Transport Proteins; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D015870:Gene Expression; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D001613:beta 2-Microglobulin / Q000235:genetics
chemical_list: D000199:Actins; D000998:Antiviral Agents; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C107608:FABP7 protein, human; D050612:Fatty Acid Transport Proteins; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D015850:Interleukin-6; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D001613:beta 2-Microglobulin; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D008071:Lipoprotein Lipase; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D003066:Coenzyme A Ligases