Sato Akira, Nemoto Hina, Yabuki Ayano, Sato Genta, Ogawa Yuta, Ohira Makoto
Department of Food and Nutritional Science, Faculty of Human Life Science, Miyagi Gakuin Women's University, Sendai, Miyagi, Japan.
Faculty of Pharmacy, Iryo Sosei University, Iwaki, Fukushima, Japan.
Int J Exp Pathol. 2025 Jul;106(4):e70002. doi: 10.1111/iep.70002.
Ketone bodies (KBs), which include β-hydroxybutyric acid (β-HB) and acetoacetic acid (AcAc), play critical roles in organismal energy homeostasis; however, their effects on atherosclerosis remain unknown. In this study, we investigated the role of β-HB and AcAc on proliferation and lipid accumulation in macrophages by the uptake of oxidized LDL (Ox-LDL), causing the formation of atherosclerotic plaques, using mouse macrophage J774A.1 cells. Both β-HB and AcAc reduced cell proliferation, and AcAc increased lipid accumulation in Ox-LDL-treated J774A.1 cells. Western blotting showed that Ox-LDL decreased the protein expression of two KB-specific receptors, GPR41 and GPR43, both of which are known as potent modulators of inflammation, but had negligible effects on that of the β-HB-specific GPR109A in the cells. These results suggest that Ox-LDL may induce inflammatory responses by decreasing the protein expression of GPR41 and GPR43 in macrophages, and that AcAc, but not β-HB, may exacerbate Ox-LDL-caused atherosclerosis.
酮体（KBs），包括β-羟基丁酸（β-HB）和乙酰乙酸（AcAc），在机体能量稳态中发挥关键作用；然而，它们对动脉粥样硬化的影响仍不清楚。在本研究中，我们使用小鼠巨噬细胞J774A.1细胞，通过摄取氧化低密度脂蛋白（Ox-LDL）导致动脉粥样硬化斑块形成，研究了β-HB和AcAc对巨噬细胞增殖和脂质积累的作用。β-HB和AcAc均降低了细胞增殖，且AcAc增加了Ox-LDL处理的J774A.1细胞中的脂质积累。蛋白质印迹法显示，Ox-LDL降低了两种KB特异性受体GPR41和GPR43的蛋白表达，这两种受体均为已知的强效炎症调节剂，但对细胞中β-HB特异性GPR109A的蛋白表达影响可忽略不计。这些结果表明，Ox-LDL可能通过降低巨噬细胞中GPR41和GPR43的蛋白表达诱导炎症反应，且AcAc而非β-HB可能加剧Ox-LDL所致的动脉粥样硬化。
