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.
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.
Kannisto
Katja
K
Department of Medicine, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden.
Sutinen
Jussi
J
Korsheninnikova
Elena
E
Fisher
Rachel M
RM
Ehrenborg
Ewa
E
Gertow
Karl
K
Virkamäki
Antti
A
Nyman
Tuulikki
T
Vidal
Hubert
H
Hamsten
Anders
A
Yki-Järvinen
Hannele
H
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
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