화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.503, No.4, 3044-3049, 2018
Effects of telmisartan on TNF alpha induced PPAR gamma phosphorylation and insulin resistance in adipocytes
Background: Telmisartan is an angiotensin II receptor blocker (ARB) and a partial agonist of peroxisome proliferator activated receptor gamma (PPAR gamma). It has been shown to significantly enhance insulin sensitivity in clinical studies and in vitro experiments. However, the effect of telmisartan on PPAR gamma in adipocytes remains unknown. Methods: 3T3-L1 adipocytes were incubated with tumor necrosis factor alpha (TNF alpha) 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 PPAR gamma, glucose uptake, mRNA levels of PPAR gamma downstream genes and adiponectin secretion of adipocytes were analyzed. Results: Telmisartan reduced the phosphorylation level of PPAR gamma, 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 TNF alpha stimulation. Conclusions: Telmisartan regulated PPAR gamma phosphorylation and its downstream gene expressions, promoted glucose uptake and acted as an overall insulin sensitizing agent in adipocytes. The specific phosphorylation site of PPAR gamma affected by telmisartan, the mechanism of telmisartan in regulating PPAR gamma phosphorylation, and whether the effects of telmisartan in adipocytes is responsible for its whole-body insulin sensitizing effect require further exploration. (C) 2018 Elsevier Inc. All rights reserved.