Effects of telmisartan on TNFα induced PPARγ phosphorylation and insulin resistance in adipocytes

Abstract

BackgroundTelmisartan is an angiotensin II receptor blocker (ARB) and a partial agonist of peroxisome proliferator activated receptor γ (PPARγ). It has been shown to significantly enhance insulin sensitivity in clinical studies and in vitro experiments. However, the effect of telmisartan on PPARγ in adipocytes remains unknown. Methods3T3-L1 adipocytes were incubated with tumor necrosis factor α (TNFα) to simulate growth under an inflammatory condition. On this basis, adipocytes were treated with telmisartan at different concentrations for 1 h. Then, the phosphorylation level of PPARγ, glucose uptake, mRNA levels of PPARγ downstream genes and adiponectin secretion of adipocytes were analyzed. ResultsTelmisartan reduced the phosphorylation level of PPARγ, altered mRNA expressions of adiponectin, adipsin, leptin, FABP4, GLUT4 and CAP, and promoted the secretion of adiponectin. Furthermore, telmisartan treatment restored the decrease of cellular glucose uptake due to TNFα stimulation. ConclusionsTelmisartan regulated PPARγ phosphorylation and its downstream gene expressions, promoted glucose uptake and acted as an overall insulin sensitizing agent in adipocytes. The specific phosphorylation site of PPARγ affected by telmisartan, the mechanism of telmisartan in regulating PPARγ phosphorylation, and whether the effects of telmisartan in adipocytes is responsible for its whole-body insulin sensitizing effect require further exploration.