HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV- 1/HAART-associated lipodystrophy.
BACKGROUND
The aetiopathogenic bases of HIV-l-/highly active antiretroviral treatment (HAART)-associated lipodystrophy (HALS) are poorly known, but this syndrome indicates that adipose tissue is highly sensitive to either HIV-1 infection, antiretroviral drugs or their combination.


METHODS
To assess the relative contribution of infection and drugs, we compared the expression of marker genes corresponding to mitochondrial function, adipocyte differentiation and metabolism, and adipokines in subcutaneous adipose tissue from healthy controls, untreated HIV-1-infected patients, and HIV-1-infected patients treated with HAART with or without HALS.


RESULTS
Subcutaneous adipose tissue from HIV-1-infected patients contained lower concentrations of the mRNA of the mitochondrial DNA-encoded cytochrome c oxidase subunit II than that of controls. These concentrations decreased further in association with HAART. The expression of nuclear genes coding for mitochondrial proteins, peroxisome proliferator-activated receptor-y, and adipocyte-specific markers was reduced in HIV-1-infected patients, treated or not, with respect to the controls. In contrast, the mRNA concentrations of uncoupling protein-3 and preadipocyte factor-1 increased in lipody-strophic HAART-treated patients. The genes coding for adipokines were strongly affected: tumour necrosis factor-alpha was upregulated, whereas adiponectin and leptin were downregulated in HIV-1-infected patients, treated or not. Thus, substantial alterations of gene expression were already present when naive patients were compared with controls. Further changes were associated with HAART and with the diagnosis of HALS.


CONCLUSIONS
Disturbances in adipose tissue gene expression are already present in untreated HIV-1-infected patients, thus indicating a role of HIV-1 infection itself in eliciting adipose tissue alterations that are worsened by HAART, which ultimately leads to HALS.
Giralt
Marta
M
Department de Bioquimica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain. mgiralt@ub.edu
Domingo
Pere
P
Guallar
Jordi P
JP
Rodriguez de la Concepción
M Luísa
ML
Alegre
Marta
M
Domingo
Joan C
JC
Villarroya
Francesc
F
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000378:metabolism
D011506:Proteins