Telmisartan Improves Insulin Resistance and Modulates Adipose Tissue Macrophage Polarization in High-Fat-Fed Mice

• DOI: 10.1210/en.2010-1312
• Publication Date: 2011-03-23T02:33:08Z
• Authors: Shiho Fujisaka; Isao Usui; Yukiko Kanatani; Masashi Ikutani; Ichiro Takasaki; Koichi Tsuneyama; Yoshiaki Tabuchi; Agussalim Bukhari; Yu Yamazaki; Hikari Suzuki; Satoko Senda; Aminuddin Aminuddin; Yoshinori Nagai; Kiyoshi Takatsu; Masashi Kobayashi; Kazuyuki Tobe
• Keywords: Epididymis; 0301 basic medicine; Gene Expression Profiling; Body Weight; Antigens, Differentiation, Myelomonocytic; Flow Cytometry; Benzoates; Dietary Fats; CD11c Antigen; 3. Good health; 03 medical and health sciences; Glucose; Adipose Tissue; Gene Expression Regulation; Antigens, CD; Adipocytes; Animals; Benzimidazoles; Lectins, C-Type; Insulin Resistance; Angiotensin II Type 1 Receptor Blockers; Cell Adhesion Molecules; Cell Size

Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-γ agonist, reportedly has more beneficial effects on insulin sensitivity than other angiotensin II type 1 receptor blockers. In this study, we studied the effects of telmisartan on the adipose tissue macrophage phenotype in high-fat-fed mice. Telmisartan was administered for 5 wk to high-fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in visceral adipose tissues were then examined. An insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight, and adipocyte size without affecting the amount of energy intake. Telmisartan reduced the mRNA expression of CD11c and TNF-α, M1 macrophage markers, and significantly increased the expressions of M2 markers, such as CD163, CD209, and macrophage galactose N-acetyl-galactosamine specific lectin (Mgl2), in a quantitative RT-PCR analysis. A flow cytometry analysis showed that telmisartan decreased the number of M1 macrophages in visceral adipose tissues. In conclusion, telmisartan improves insulin sensitivity and modulates adipose tissue macrophage polarization to an antiinflammatory M2 state in high-fat-fed mice.