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

• Published in: Biochemical and biophysical research communications Vol. 503; no. 4; pp. 3044 - 3049
• Main Authors: Fang, Tao, Di, Yanbo, Li, Guangkuo, Cui, Xiaoxu, Shen, Na, Li, Yonghui, Xi, Peiqi, Xie, Yun, Tian, Fengshi, Li, Guangwei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.09.2018
• Subjects: 3T3-L1 Cells; 60 APPLIED LIFE SCIENCES; Adipocytes - drug effects; Adipocytes - immunology; ANGIOTENSIN; Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; INSULIN; Insulin Resistance; Mice; PHOSPHORYLATION; Phosphorylation - drug effects; PPAR gamma - immunology; PPARγ phosphorylation; RECEPTORS; Telmisartan; Telmisartan - pharmacology; TNFα; Tumor Necrosis Factor-alpha - immunology; Insulin resistance; TNFα; PPARγ phosphorylation; Telmisartan
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.08.091

Telmisartan 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. 3T3-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. Telmisartan 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. Telmisartan 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. •Telmisartan treatment alleviates insulin resistance in adipocytes stimulated with TNFα.•Telmisartan treatment reduces phosphorylation of PPARγ in adipocytes stimulated with TNFα.•Telmisartan treatment regulates the expressions of PPARγ downstream genes.•Telmisartan treatment promotes the secretion of adiponectin in adipocytes.