10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 6-8 November 2008, London, UK

DIFFERENTIAL ALTERATIONS OF GENE EXPRESSION IN VISCERAL VERSUS SUBCUTANEOUS ADIPOSE TISSUE FROM HIV-1-INFECTED, HAART-TREATED PATIENTS WITH LIPODYSTROPHY: A PILOT STUDY

Antiviral Therapy 2008; 13(Suppl. 4):A3 (abstract no. O-01)

J Villarroya¹, JM Gallego-Escuredo¹, JC Domingo¹, M Alegre², MM Gutierrez², MG Mateo², F Villarroya¹, P Domingo² and M Giralt^1
1University of Barcelona, Barcelona, Spain; ²Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

AIM: Opposite alterations (lipoatrophy versus hypertrophy) are often observed in subcutaneous (SCA) versus visceral (VSA) adipose tissue in HIV type-1 (HIV-1)-infected, highly active antiretroviral therapy (HAART)-treated patients with lipodystrophy. Although the molecular alterations in SCA from these patients have been studied previously, no data is available on gene expression disturbances in VSA because of the difficult availability of such adipose samples. The present pilot study takes advantage of the availability of seven samples of VSA from HIV-1-infected, HAART-treated patients with lipodystrophy collected after minor surgery. The objective was to compare gene expression alterations in SCA and VSA depots to gain insight in their differential responsiveness to HIV-1 infection and antiretroviral treatment.

METHODS: SCA from 10 and VSA from 7 HIV-1-infected, HAART-treated patients with lipodystrophy as well as SCA and VSA from 10 non-infected control individuals were analysed. Four samples from the patient groups corresponded to double biopsies of SCA and VSA from the same patient. Main patterns of sex and age distribution, cumulative antiretroviral treatment pattern (including nucleoside reverse transcriptase inhibitors, such as stavudine or zidovudine, as well as protease inhibitors) and systemic metabolic alterations (lipidaemia and HOMA) were not significantly different between the patient groups.

RESULTS: Mitochondrial DNA levels were decreased in SCA and VSA from patients with respect to their corresponding controls. A similar profile of decrease in both depots was observed for mitochondrial mRNA levels. The increase in mitochondrial protein amount already described in SCA from patients was equally observed in VSA from patients, as shown by increased levels of COXIV and ATP synthase-α measured using immunoblotting. In contrast, the mRNAs for markers of adipogenic differentiation and metabolism, such as PPARγ, adiponectin, GLUT4 and lipoprotein lipase, were lowered in SCA from patients, whereas they remained unaltered in VSA from patients with respect to controls. Concerning markers of inflammation, tumour necrosis factor-α mRNA was increased in SCA from patients and a similar induction was observed in VSA from patients. The same occurred for CD68 mRNA, indicative of macrophage infiltration and for HLA-DQα2 mRNA. This was confirmed by immunoblot analysis of ß2-microglobulin levels that was induced both in SCA and VSA from patients.

CONCLUSIONS: To our knowledge, this is the first study in which a gene expression analysis of VSA from HIV-1infected, HAART-treated patients with lipodystrophy is reported. Similar alterations in markers of mitochondrial function and inflammation in SCA and VSA from patients suggest that these processes are unlikely to be the main determinants of the differential behaviour of the two adipose depots in patients. No impairment in gene expression for marker genes of adipogenesis in VSA is consistent with the lack of atrophy of this depot and highlights the relevance of the adipogenic differentiation processes in the outcome of adipose tissue depots in response to viral and drug-induced insults.

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2008-11-06
O-01

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