Wada Toshiaki, Senokuchi Takafumi, Shi Yudan, Furusho Tatsuya, Morita Yutaro, Sarie Maeda, Hanatani Satoko, Fukuda Kazuki, Ishii Norio, Matsumura Takeshi, Fujiwara Yukio, Komohara Yoshihiro, Araki Eiichi, Kubota Naoto
Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Atherosclerosis. 2025 Feb;401:119088. doi: 10.1016/j.atherosclerosis.2024.119088. Epub 2024 Dec 12.
Oral administration of acetic acid, a short-chain fatty acid, has been shown to efficiently reduce obesity and insulin resistance in both experimental animals and humans. The anti-atherosclerotic effect of acetate is expected owing to its anti-inflammatory and anti-oxidative stress characteristics; however, this remains to be fully understood.
For 12 weeks, apolipoprotein E-deficient mice were administered 0.6 % sodium acetate water or vehicle water. Plaque formation and progression were investigated using histological analysis of dissected aortic root sections. Flow cytometry and gene expression analyses were employed to assess plaque macrophage characteristics and functional states. In vitro tests were performed on mouse peritoneal primary macrophages and bone marrow-derived macrophages isolated from wild-type or GPR43-deficient mice.
Atherosclerotic plaque formation was inhibited in acetate-treated ApoE-deficient mice, and AMPK activation was directly validated in plaque macrophages. Acetate inhibited macrophage proliferation, reactive oxygen species production, and pro-inflammatory molecule expression, all of which were reversed by AMPK inhibition. Bone marrow transplantation study revealed the role of GPR43-mediated AMPK activation by acetic acid in anti-atherosclerotic effect.
Oral acetate administration suppressed arteriosclerosis formation and progression in ApoE-deficient mice. Acetate inhibited macrophage proliferation, inflammatory cytokine release, and reactive oxygen species production via GPR43-mediated AMPK activation in macrophages, ameliorating plaque formation and progression.
已表明口服短链脂肪酸醋酸可有效减轻实验动物和人类的肥胖及胰岛素抵抗。由于醋酸具有抗炎和抗氧化应激特性，预计其具有抗动脉粥样硬化作用；然而，这一点仍有待充分了解。
对载脂蛋白E缺陷小鼠给予0.6%醋酸钠水溶液或赋形剂水溶液，持续12周。通过对解剖的主动脉根部切片进行组织学分析来研究斑块形成和进展情况。采用流式细胞术和基因表达分析来评估斑块巨噬细胞的特征和功能状态。对从野生型或GPR43缺陷小鼠分离的小鼠腹腔原代巨噬细胞和骨髓来源巨噬细胞进行体外试验。
醋酸处理的载脂蛋白E缺陷小鼠的动脉粥样硬化斑块形成受到抑制，且在斑块巨噬细胞中直接验证了AMPK的激活。醋酸抑制巨噬细胞增殖、活性氧生成和促炎分子表达，而AMPK抑制可逆转所有这些作用。骨髓移植研究揭示了醋酸通过GPR43介导的AMPK激活在抗动脉粥样硬化作用中的作用。
口服醋酸可抑制载脂蛋白E缺陷小鼠的动脉硬化形成和进展。醋酸通过巨噬细胞中GPR43介导的AMPK激活抑制巨噬细胞增殖、炎性细胞因子释放和活性氧生成，改善斑块形成和进展。
