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9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV19-21 July 2007, Sydney, Australia |
THE EFFECT OF ANTIRETROVIRAL THERAPY ON GENES INVOLVED WITH GLUCOSE AND LIPID METABOLISM
ANTIVIRAL THERAPY 2007; 12(Suppl. 2):L12 (abstract no. O-14)
M Boothby1, JW Tomlinson2, KC McGee3, S Das4, LL Gathercole2, AL Harte3, P Higgins3, CM Kusminski3, PG McTernan3 and M Shahmanesh1
1University Hospital Birmingham, Birmingham, UK; 2University of Birmingham, Birmingham, UK; 3Warwick University, Warwick, UK; 4University Hospitals Coventry and Warwicshire, Coventry, UK
OBJECTIVES: To compare patterns of gene expression in the subcutaneous adipose tissue of HIV-positive subjects before and after 6 months of antiretroviral therapy with HIV-negative controls.
METHODS: Subcutaneous fat biopsies from the iliac crest were performed on 18 HIV-positive patients and 10 HIV- negative controls. Following total RNA extraction, gene expression was profiled using real-time PCR and quantified relative to an internal house-keeping gene (18S). Genes were involved in adipocyte differentiation, lipid metabolism, and glucocorticoid metabolism. HIV-positive patients were tested before, and 6 months after being randomized to either zidovudine/lamivudine or tenofovir/ emtricitabine with efavirenz. Comparison between groups was by t-tests and Mann–Whitney test.
RESULTS: Controls and patients were matched for sex and ethnicity. There were no differences in BMI, whole body DEXA and abdominal CT scans. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1), which regenerates active glucocorticoid cortisol from inactive cortisone, is reduced in treatment-naïve patients compared with controls but increases following treatment. ARV treatment increased mRNA expression of adipocyte differentiation markers and genes involved with glucose and lipid metabolism, including lipoprotein lipase (LPL) hormone-sensitive lipase (HSL), fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), glucocorticoid receptor-α (GRα), and glucose transport protein (GLUT4). HOMA levels were similar between groups.
| Table 1. Fold change in gene expression from HIV-negative controls (control=1) (Abstract O-14) | |||
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| Gene | Naïve HIV | 6 months | P-value |
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| 11β HSD1 | 0.38 | 1.06 | 0.006*, 0.001† |
| H6PDH | 0.64 | 1.41 | NS |
| FAS | 0.85 | 5.3 | 0.00004† |
| LPL | 0.92 | 2.69 | 0.0002† |
| HSL | 1.22 | 4.94 | 0.0005† |
| FABP4 | 1.1 | 3.56 | 0.00006† |
| GRα | 1.05 | 2.81 | 0.00007† |
| GLUT-4 | 1.4 | 2.78 | 0.004† |
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| *naïve versus control; †naïve versus 6 months. NS, not significant. H6PDH, hexose-6-phosphate dehydrogenase. | |||
CONCLUSION: 11β-HSD1 mRNA expression is decreased in HIV patients, but increases after ARV treatment alongside markers of adipocyte differentiation, lipid and glucose metabolism. We speculate that enhanced local generation of cortisol through increased 11β-HSD1 expression may underpin these observations.
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2007-07-24
O-14
Copyright © 2007 - International Medical Press Ltd. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Medical Editor, International Medical Press, 36 St Mary-at-Hill, London EC3R 8DU, United Kingdom.