Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro

Pushpakom, S.P., Adaikalakoteswari, A. ORCID: 0000-0003-2974-3388, Owen, A., Back, D.J., Tripathi, G., Kumar, S., McTernan, P. ORCID: 0000-0001-9023-0261 and Pirmohamed, M., 2018. Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro. Diabetes and Vascular Disease Research. ISSN 1479-1641

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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
Publication Title: Diabetes and Vascular Disease Research
Creators: Pushpakom, S.P., Adaikalakoteswari, A., Owen, A., Back, D.J., Tripathi, G., Kumar, S., McTernan, P. and Pirmohamed, M.
Publisher: Sage
Date: 21 February 2018
ISSN: 1479-1641
Identifiers:
NumberType
10.1177/1479164118757924DOI
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 14 Mar 2018 16:27
Last Modified: 14 Mar 2018 16:27
URI: http://irep.ntu.ac.uk/id/eprint/32982

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