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



Pushpakom, Sudeep P ORCID: 0000-0002-6682-4235, Adaikalakoteswari, Antonysunil, Owen, Andrew ORCID: 0000-0002-9819-7651, Back, David J, Tripathi, Gyanendra, Kumar, Sudhesh, McTernan, Philip and Pirmohamed, Munir ORCID: 0000-0002-7534-7266
(2018) Telmisartan reverses antiretroviral-induced adipocyte toxicity and insulin resistance in vitro. Diabetes & vascular disease research, 15 (3). 233 - 242.

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Abstract

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.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.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.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: Article
Depositing User: Symplectic Admin
Date Deposited: 16 Mar 2018 11:35
Last Modified: 04 Nov 2020 00:20
DOI: 10.1177/1479164118757924
Related URLs:
URI: http://livrepository.liverpool.ac.uk/id/eprint/3019103