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 pAkt. 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.
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| http://dx.doi.org/10.1177/1479164118757924 | DOI Listing |
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