The Library
Evidence for a shift to anaerobic metabolism in adipose tissue in efavirenz-containing regimens for HIV with different nucleoside backbones
Tools
Tools
Tools
McGee, K. C., Shahmanesh, Mohsen, Boothby, Meg, Nightingale, Peter, Gathercole, Laura L., Tripathi, Gyanendra, Harte, Alison L., Shojaee-Moradie, Fariba, Umpleby, A Margot, Das, Satyajit, Al-Daghri, Nasser M., McTernan, P. G. and Tomlinson, Jeremy W. (2011) Evidence for a shift to anaerobic metabolism in adipose tissue in efavirenz-containing regimens for HIV with different nucleoside backbones. Antiviral Therapy, Volume 17 (Number 3). pp. 495-507. doi:10.3851/IMP2017 ISSN 1359-6535.
Research output not available from this repository.
Request-a-Copy directly from author or use local Library Get it For Me service.
Official URL: http://dx.doi.org/10.3851/IMP2017
Abstract
BACKGROUND:
Antiretroviral (ARV) treatment has been associated with abnormalities in lipid and mitochondrial metabolism. We compared patterns of gene expression in the subcutaneous adipose tissue (SAT) of HIV-positive subjects before and after 18-24 months of ARV therapy with HIV-negative controls.
METHODS:
HIV patients naive to ARV were randomized to receive zidovudine (AZT), lamivudine (3TC) with efavirenz (EFV) or tenofovir disoproxil fumarate (TDF) with emtricitabine (FTC) and EFV. Healthy controls (n=15) were matched for age, ethnicity and gender. Patients on a regimen containing abacavir (ABC), 3TC and EFV for 18-24 months were also tested. Genes involved in adipocyte glucocorticoid, lipid and mitochondrial metabolism, and adipocyte differentiation, were profiled with real-time PCR.
RESULTS:
AZT led to increased visceral adipose tissue (VAT; P=0.012) and VAT:SAT ratio (P=0.036), whereas TDF increased SAT (P=0.047) and peripheral fat/lean body mass ratio (P=0.017). HIV treatment-naive patients had lower plasma lipoprotein lipase (LPL) activity (P=0.0001) versus controls (remaining below controls after ARV; P=0.038-0.0001). The overall pattern of gene expression was similar across all treatment groups, being most marked with AZT and least with TDF. There was up-regulation of peroxisome proliferator-activated receptor-γ coactivator-1α, uncoupling protein-2 and hexose 6-phosphate dehydrogenase, and down-regulation of nuclear respiratory factor-1, cytochrome oxidase B, cytochrome c oxidase-4, uncoupling protein-3, 11β-hydroxysteroid dehydrogenase type-1, glucocorticoid receptor-α, fatty acid synthase, fatty acid binding protein-4, LPL and hormone sensitive lipase (18-24 months post-treatment versus pretreatment levels and controls; P<0.05 to <0.0001).
CONCLUSIONS:
The decreased expression of genes involved in lipid and mitochondrial metabolism 18-24 months post-ARV treatment in SAT of HIV patients, in conjunction with the increase in uncoupling protein-2 and decrease in cytochrome oxidase B gene expression, provides evidence of mitochondrial dysfunction and a shift to anaerobic metabolism within SAT in EFV-containing ARV regimens.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
| Journal or Publication Title: | Antiviral Therapy | ||||
| Publisher: | International Medical Press | ||||
| ISSN: | 1359-6535 | ||||
| Official Date: | 2011 | ||||
| Dates: |
|
||||
| Volume: | Volume 17 | ||||
| Number: | Number 3 | ||||
| Page Range: | pp. 495-507 | ||||
| DOI: | 10.3851/IMP2017 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
