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Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro
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Pushpakom, S. P., Adaikalakoteswari, Antonysunil, Owen, A., Back, D. J., Tripathi, Gyanendra, Kumar, Sudhesh, McTernan, P. G. and Pirmohamed, M. (2018) Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro. Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease, 15 (3). pp. 233-242. doi:10.1177/1479164118757924
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Official URL: https://doi.org/10.1177/1479164118757924
Abstract
Background:
Antiretroviral therapy in HIV-positive patients leads to insulin resistance which is central to the pathogenesis of various metabolic abnormalities and cardiovascular disease seen in this patient group. We have investigated the dose–response relationship of telmisartan, an antihypertensive, on adipocytes in vitro in order to determine whether it may have metabolic beneficial effects.
Methods:
Using in vitro chronic toxicity models (3T3-F442A murine and primary human adipocytes), we evaluated the effects of different concentrations of telmisartan on adipocyte differentiation and adipogenic gene expression using lipid accumulation assays and real-time polymerase chain reaction, respectively. Adipokine secretion and expression of insulin signalling mediators were evaluated using enzyme-linked immunosorbent assays.
Results:
Telmisartan partially reversed the deleterious effects of antiretrovirals on adipocyte lipid accumulation, expression of adipogenic regulators (peroxisome proliferator receptor-gamma and lipin 1), adipokine secretion and expression of the insulin signalling mediator pAktSer473. The metabolic effects of telmisartan followed a non-monotonic response with the maximal effect observed at 5 µM in the primary human adipocyte model.
Conclusion:
Telmisartan has beneficial metabolic effects in adipocytes in vitro, but its potential to reduce antiretroviral-induced cardiometabolic disease in HIV-infected individuals needs to be evaluated in a well-designed adequately powered clinical trial.
| Item Type: | Journal Article | ||||||||
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| Subjects: | R Medicine > RC Internal medicine | ||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School | ||||||||
| Library of Congress Subject Headings (LCSH): | Antiretroviral agents, HIV infections -- Treatment, Insulin resistance, Hypotensive agents, Metabolism -- Disorders, Fat cells | ||||||||
| Journal or Publication Title: | Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease | ||||||||
| Publisher: | Sage Publications Ltd. | ||||||||
| ISSN: | 1479-1641 | ||||||||
| Official Date: | 1 May 2018 | ||||||||
| Dates: |
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| Date of first compliant deposit: | 1 March 2018 | ||||||||
| Volume: | 15 | ||||||||
| Number: | 3 | ||||||||
| Page Range: | pp. 233-242 | ||||||||
| DOI: | 10.1177/1479164118757924 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| RIOXX Funder/Project Grant: |
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| Open Access Version: |
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