Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice

Abstract

Purpose: Recent studies suggest that exchange of macrophage phenotype (M1/M2) in adipose tissue is associated with chronic low-grade inflammation in obesity. M1 macrophages enhance a chronic inflammatory state in adipose tissues, whereas M2 macrophages inhibit it. Although exercise training might inhibit pro-inflammatory cytokine gene expression in adipose tissue, it remains unclear whether exercise training affects the phenotypic switch of macrophage polarization in adipose tissue. Therefore, we investigated the effect of exercise training on the macrophage phenotypic switch in adipose tissue in high-fat-induced obese mice. Methods: Male C57BL/6 mice were divided into four groups; normal diet (ND) control (n=7), ND exercise (n=7), high-fat-diet (HFD) control (n=12), and HFD exercise (n=12) groups. All exercised mice ran on a treadmill at 12-20 m/min for 60 min/day for 16 weeks. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, F4/80, monocyte chemotactic protein (MCP)-1, CXCL14, inter-cellular adhesion molecule (ICAM)-1, vascular-cellular adhesion molecule (VCAM)- I, CD11c, CD163 and toll-like receptor (TLR)4 mRNA expressions in adipose tissue were evaluated by real time-RT-PCR. Results: In HFD mice, exercise training did not induce loss of body or adipose tissue mass, exercise training nevertheless markedly inhibited TNF-alpha and F4/80 mRNA expression in adipose tissue. The exercise training attenuated HFD-induced increase in ICAM-I mRNA expression, but not MCP-1, CXCL14 and VCAM-1 mRNA expressions. In addition, increased CD11c mRNA expression, which is a M1 macrophage specific marker, with HFD treatment was attenuated by exercise training. In contrast, although the mRNA expression of CD163, a M2 macrophage specific marker, in adipose tissue was significantly decreased by HFD, the exercise training significantly increased its expression. Also, the higher mRNA expression of TLR4, which induces pro-inflammatory cytokine production after fatty acid recognition, was strongly inhibited by the exercise training in HFD mice. Conclusion: Exercise training might induce the phenotypic switching from M1 macrophage to M2 macrophage in obese adipose tissue besides inhibiting M1 macrophage infiltration into adipose tissue. Therefore, chronic exercise might contribute to inhibit inflammation in adipose tissue via down regulation of TLR4.