ABSTRACT: Genome-wide changes in subcutaneous adipose tissue expression in HIV negative adults after 2 weeks of zidovudine or stavudine with lamivudine.
Project description:As controversy remains as to the exact mechanisms by which the thymidine-analogue nucleoside reverse transcriptase inhibitors, zidovudine (AZT) and stavudine (d4T) induce subcutaneous adipose tissue toxicity, we used microarrays to dentify patterns of gene expression in human subcutaneous adipose tissue that change as a result of exposure to these drugs for 2 weeks. Paired RNA samples (baseline and week 2), isolated from the adipose tissue of HIV-uninfected healthy adults randomized to 6 weeks of either AZT/ lamivudine (3TC) or d4T/ 3TC were analysed by microarray.
Project description:As controversy remains as to the exact mechanisms by which the thymidine-analogue nucleoside reverse transcriptase inhibitors, zidovudine (AZT) and stavudine (d4T) induce subcutaneous adipose tissue toxicity, we used microarrays to dentify patterns of gene expression in human subcutaneous adipose tissue that change as a result of exposure to these drugs for 2 weeks.
Project description:This study investigated longitudinal changes in adipose tissue–derived extracellular vesicle protein cargo, referred to as adiposomes, following bariatric surgery in adults with obesity. 23 adults with obesity scheduled for sleeve gastrectomy were enrolled. Subcutaneous adipose tissue samples and clinical cardiometabolic measurements were collected before surgery and again approximately 12–14 weeks after surgery.
Project description:Exploratory microarray analysis identified significant changes in gene expression in adipose tissue. These included changes in genes regulating lipid and steroid metabolic processes and electron carrier activity in HIV-infected patients receiving antiretroviral therapy (ART). Additional genes involved in metabolic processes and mitochondrial function were found to be up-regulated in the adipose tissue of HIV-positive patients compared with HIV-negative controls. To identify differential gene expression in different tissues (PBMC, muscle, adipose tissue) between HIV patient groups (HIV negative, HIV positive with ART, HIV positive without ART).
Project description:We used microarrays to detail the global gene expression profile in subcutaneous adipose tissue between controls and HIV-infected patients under antiretroviral treatment. Subcutaneous adipose tissue biopsy from 7 HIV-infected patients and 6 control subjects were taken for RNA extraction and hybridization on Affymetrix microarrays.
Project description:Exploratory microarray analysis identified significant changes in gene expression in adipose tissue. These included changes in genes regulating lipid and steroid metabolic processes and electron carrier activity in HIV-infected patients receiving antiretroviral therapy (ART). Additional genes involved in metabolic processes and mitochondrial function were found to be up-regulated in the adipose tissue of HIV-positive patients compared with HIV-negative controls.
Project description:A new mechanism is proposed for the apparent breakthrough of HIV that occurs approximately 6 months after the commencement of therapy with zidovudine (AZT). Using a simple mathematical model of the interacting population dynamics of HIV and its major host cell in the circulation (the CD4+ lymphocyte), predicted patterns of HIV plasma viraemia in the weeks following treatment with zidovudine are generated. These are in close agreement with observed patterns despite the fact that the model contains no mechanisms for the development of drug-resistant strains of virus. It is suggested that the patterns of viral abundance observed during the first 6 months after treatment may be the result of non-linearities in the interactions between HIV and CD4+ cells, and that it is only after the first post-treatment burst of viral production that drug resistance plays an important role.
Project description:We used microarrays to detail the global gene expression profile in subcutaneous adipose tissue between controls and HIV-infected patients under antiretroviral treatment.
Project description:Although the rate of fatty acid release from adipose tissue into the systemic circulation is very high in most obese adults, some obese adults maintain relatively low rates of fatty acid release, which helps protect them against the development of systemic insulin resistance. The primary aim of this study was to identify factors in adipose tissue that may underlie low vs. high rates of fatty acid mobilization in a relatively homogeneous cohort of obese adults. We obtained subcutaneous abdominal adipose tissue samples from 30 obese adults (BMI: 38±1 kg/m2, age: 30±2 yr) after an overnight fast. We performed microarray analysis on the adiose tissue samples.
Project description:Background and objective: Combination antiretroviral therapy (cART) is associated with lipodystrophy i.e. loss of subcutaneous adipose tissue in abdomen, limbs and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulates in this region (“buffalo hump”). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1-infected cART-treated patients with (cART+LD+) and without (cART+LD-) lipodystrophy. Results: Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA, copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD-. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical vs. abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. Conclusions: As mtDNA is depleted even in the non-atrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal s.c. adipose tissue is in expression of homeobox genes. We used histology, microarray, polymerase chain reaction and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n=21) and cART+LD- (n=11). The study consists of 17 patients on antiretroviral treatment who have developed lipodystrophy and 11 patients that are on similar treatment but have not developped lipodystrophy. All patients are HIV+ and have 2 adipose tissue samples taken from them (dorsocervical+abdominal).
