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HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV- 1/HAART-associated lipodystrophy.
Antivir Ther. 2006; 11(6):729-40.AT

Abstract

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.

Authors+Show Affiliations

Department de Bioquimica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain. mgiralt@ub.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17310817

Citation

Giralt, Marta, et al. "HIV-1 Infection Alters Gene Expression in Adipose Tissue, Which Contributes to HIV- 1/HAART-associated Lipodystrophy." Antiviral Therapy, vol. 11, no. 6, 2006, pp. 729-40.
Giralt M, Domingo P, Guallar JP, et al. HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV- 1/HAART-associated lipodystrophy. Antivir Ther (Lond). 2006;11(6):729-40.
Giralt, M., Domingo, P., Guallar, J. P., Rodriguez de la Concepción, M. L., Alegre, M., Domingo, J. C., & Villarroya, F. (2006). HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV- 1/HAART-associated lipodystrophy. Antiviral Therapy, 11(6), 729-40.
Giralt M, et al. HIV-1 Infection Alters Gene Expression in Adipose Tissue, Which Contributes to HIV- 1/HAART-associated Lipodystrophy. Antivir Ther (Lond). 2006;11(6):729-40. PubMed PMID: 17310817.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV- 1/HAART-associated lipodystrophy. AU - Giralt,Marta, AU - Domingo,Pere, AU - Guallar,Jordi P, AU - Rodriguez de la Concepción,M Luísa, AU - Alegre,Marta, AU - Domingo,Joan C, AU - Villarroya,Francesc, PY - 2007/2/22/pubmed PY - 2007/3/16/medline PY - 2007/2/22/entrez SP - 729 EP - 40 JF - Antiviral therapy JO - Antivir. Ther. (Lond.) VL - 11 IS - 6 N2 - 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. SN - 1359-6535 UR - https://www.unboundmedicine.com/medline/citation/17310817/HIV_1_infection_alters_gene_expression_in_adipose_tissue_which_contributes_to_HIV__1/HAART_associated_lipodystrophy_ L2 - http://www.diseaseinfosearch.org/result/4261 DB - PRIME DP - Unbound Medicine ER -