Effect of telmisartan on the therapeutic efficacy of pitavastatin in high-fat diet induced dyslipidemic guinea pigs

摘要

Angiotensin II-receptor blockers (ARBs), similar to HMG-CoA reductase inhibitors (statins), could improve lipid metabolism abnormalities. There might be some cross-talking pathways between statins and ARBs to produce additive beneficial effects on lipid metabolism in dyslipidemia. However, few studies investigate the effects of ARBs on the therapeutic efficacy of statins in dyslipidemia. The present study was designed to systematically evaluate the effects of telmisartan on the therapeutic efficacy of pitavastatin on lowering lipid level and reducing fat deposition by employing a dyslipidemia model, guinea pigs. 48 Male guinea pigs fed with high-fat diet were randomly grouped and treated with vehicle, telmisartan, pitavastatin or telmisartan/pitavastatin combinations. After treatment for eight weeks, telmisartan could significantly enhance the therapeutic efficacy of pitavastatin by extremely reducing body weight gain, weight of adipose tissue and adipocyte size. However, telmisartan/pitavastatin combinations could not further improve lipid levels on the basis of pitavastain, though single telmisartan markedly decreased triglyceride (TG) and slightly increased high density lipoprotein cholesterol (HDL-C). Moreover, telmisartan/pitavastatin combinations significantly upregulated the gene expression level of peroxisome proliferator-activated receptor (PPAR)-delta, but no effects on the expression of PPAR-alpha/gamma, leptin and adiponectin compared to monotherapy. Taken together, our studies provided new evidences that telmisartan has an additive beneficial influence on decreasing fat deposition and weight gain through PPAR-delta pathway but cannot enhance the therapeutic efficacy of pitavastatin on lowering lipid levels. The combinational administration of telmisartan and pitavastatin could be a potential therapeutic strategy for dyslipidemia related obesity and worthy of further investigation in obese animal models. (C) 2015 Elsevier B.V. All rights reserved.