Graduate School of Sport Sciences, Waseda University, Tokorozawa, Saitama, Japan.
Exerc Immunol Rev. 2010;16:105-18.
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.
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)-1, CD11c, CD163 and toll-like receptor (TLR)4 mRNA expressions in adipose tissue were evaluated by real time-RT-PCR.
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-1 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.
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.
最近的研究表明，脂肪组织中巨噬细胞表型（M1/M2）的转换与肥胖症中的慢性低度炎症有关。M1 巨噬细胞增强了脂肪组织中的慢性炎症状态，而 M2 巨噬细胞则抑制了这种状态。尽管运动训练可能会抑制脂肪组织中促炎细胞因子基因的表达，但目前尚不清楚运动训练是否会影响脂肪组织中巨噬细胞极化的表型转换。因此，我们研究了运动训练对高脂诱导肥胖小鼠脂肪组织中巨噬细胞表型转换的影响。
雄性 C57BL/6 小鼠分为四组：正常饮食（ND）对照组（n=7）、ND 运动组（n=7）、高脂肪饮食（HFD）对照组（n=12）和 HFD 运动组（n=12）。所有运动小鼠均在跑步机上以 12-20 m/min 的速度运动 60 min/天，持续 16 周。通过实时 RT-PCR 评估脂肪组织中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、F4/80、单核细胞趋化蛋白（MCP）-1、CXCL14、细胞间黏附分子（ICAM）-1、血管细胞黏附分子（VCAM）-1、CD11c、CD163 和 Toll 样受体（TLR）4mRNA 的表达。
在 HFD 小鼠中，运动训练并没有导致体重或脂肪组织量的丧失，但运动训练显著抑制了脂肪组织中 TNF-α和 F4/80mRNA 的表达。运动训练减弱了 HFD 诱导的 ICAM-1mRNA 表达的增加，但对 MCP-1、CXCL14 和 VCAM-1mRNA 表达没有影响。此外，HFD 治疗导致 CD11c mRNA 表达增加，这是 M1 巨噬细胞的特异性标志物，而运动训练则减弱了这种表达。相反，尽管脂肪组织中 CD163mRNA 的表达（M2 巨噬细胞的特异性标志物）显著降低，但运动训练显著增加了其表达。此外，在 HFD 小鼠中，脂肪酸识别后诱导促炎细胞因子产生的 TLR4 的高mRNA 表达受到运动训练的强烈抑制。
运动训练除了抑制 M1 巨噬细胞浸润脂肪组织外，还可能诱导肥胖脂肪组织中 M1 巨噬细胞向 M2 巨噬细胞的表型转换。因此，慢性运动可能通过下调 TLR4 有助于抑制脂肪组织中的炎症。
