Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka.
Laboratory of Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka.
Biol Pharm Bull. 2020;43(6):1016-1019. doi: 10.1248/bpb.b20-00078.
Endurance exercise training has been shown to induce peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in skeletal muscle. We recently reported that skeletal muscle-specific PGC-1α overexpression suppressed atherosclerosis in apolipoprotein E-knockout (ApoE) mice. β-Aminoisobutyric acid (BAIBA) is a PGC-1α-dependent myokine secreted from myocytes that affects multiple organs. We have also reported that BAIBA suppresses tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) gene expression in endothelial cells. In the present study, we hypothesized that BAIBA suppresses atherosclerosis progression, and tested that hypothesis with ApoE mice. The mice were administered water containing BAIBA for 14 weeks, and were then sacrificed at 20 weeks of age. Atherosclerotic plaque area, plasma BAIBA concentration, and plasma lipoprotein profiles were assessed. Immunohistochemical analyses of the plaque were performed to assess VCAM-1 and MCP-1 protein expression levels and macrophage infiltration. The results showed that BAIBA administration decreased atherosclerosis plaque area by 30%, concomitant with the elevation of plasma BAIBA levels. On the other hand, plasma lipoprotein profiles were not changed by the administration. Immunohistochemical analyses indicated reductions in VCAM-1, MCP-1, and Mac-2 protein expression levels in the plaque. These results suggest that BAIBA administration suppresses atherosclerosis progression without changing plasma lipoprotein profiles. We propose that the mechanisms of this suppression are reductions in both VCAM-1 and MCP-1 expression as well as macrophage infiltration into the plaque.
耐力运动训练已被证明可诱导骨骼肌中过氧化物酶体增殖物激活受体-γ共激活因子-1α（PGC-1α）的表达。我们最近报道称，骨骼肌特异性过表达 PGC-1α可抑制载脂蛋白 E 敲除（ApoE）小鼠的动脉粥样硬化。β-氨基异丁酸（BAIBA）是一种由肌细胞分泌的依赖于 PGC-1α的肌因子，可影响多个器官。我们还报道称，BAIBA 可抑制内皮细胞中肿瘤坏死因子-α诱导的血管细胞黏附分子-1（VCAM-1）和单核细胞趋化蛋白-1（MCP-1）基因的表达。在本研究中，我们假设 BAIBA 可抑制动脉粥样硬化的进展，并通过 ApoE 小鼠对此假设进行了检验。将小鼠用含有 BAIBA 的水喂养 14 周，然后在 20 周龄时处死。评估了动脉粥样硬化斑块面积、血浆 BAIBA 浓度和血浆脂蛋白谱。对斑块进行免疫组织化学分析，以评估 VCAM-1 和 MCP-1 蛋白表达水平和巨噬细胞浸润。结果表明，BAIBA 给药可使动脉粥样硬化斑块面积减少 30%，同时血浆 BAIBA 水平升高。另一方面，给药并未改变血浆脂蛋白谱。免疫组织化学分析表明，斑块中 VCAM-1、MCP-1 和 Mac-2 蛋白表达水平降低。这些结果表明，BAIBA 给药可抑制动脉粥样硬化的进展，而不改变血浆脂蛋白谱。我们提出，这种抑制的机制是 VCAM-1 和 MCP-1 表达的降低以及巨噬细胞浸润到斑块中。
