| HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV- 1/HAART-associated lipodystrophy. | |
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MedLine Citation:
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PMID: 17310817 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Marta Giralt; Pere Domingo; Jordi P Guallar; M Luísa Rodriguez de la Concepción; Marta Alegre; Joan C Domingo; Francesc Villarroya |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Antiviral therapy Volume: 11 ISSN: 1359-6535 ISO Abbreviation: Antivir. Ther. (Lond.) Publication Date: 2006 |
Date Detail:
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Created Date: 2007-02-21 Completed Date: 2007-03-15 Revised Date: 2007-03-20 |
Medline Journal Info:
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Nlm Unique ID: 9815705 Medline TA: Antivir Ther Country: England |
Other Details:
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Languages: eng Pagination: 729-40 Citation Subset: IM |
Affiliation:
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Department de Bioquimica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain. mgiralt@ub.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adipocytes
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cytology,
metabolism Adipose Tissue / cytology, metabolism* Adult Antiretroviral Therapy, Highly Active / adverse effects* Female Gene Expression Regulation* HIV Infections / drug therapy, physiopathology, virology HIV-1 / drug effects, genetics, metabolism, pathogenicity* HIV-Associated Lipodystrophy Syndrome / physiopathology*, virology Humans Male Middle Aged Mitochondria / metabolism Proteins / genetics, metabolism Subcutaneous Tissue / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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