Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Korea.
Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.
Nutrients. 2020 Feb 13;12(2):471. doi: 10.3390/nu12020471.
β-hydroxybutyrate (β-OHB) has been shown to exert an anti-inflammatory activity. Apolipoprotein-E (ApoE) is strongly associated with atherosclerosis and Alzheimer's disease (AD). This study aimed to explore the therapeutic effect of β-OHB in the brain and the aorta of high-fat diet (HFD)-fed ApoE-deficient mice. We found in Apo-E deficient mice that β-OHB attenuated lipid deposition in the choroid plexus (ChP) and decreased amyloid plaque in the substantia nigra pars compacta. We also found decreased CD68-positive macroglia infiltration of the ChP in β-OHB-treated ApoE-deficient mice. β-OHB treatment ameliorated IgG extravasation into the hippocampal region of the brain. In vitro study using ChP mice cell line revealed that β-OHB attenuated oxidized low-density lipoprotein-induced ApoE-specific differentially expressed inflammatory ChP genes. Treatment with β-OHB reduced aortic plaque formation without affecting blood lipid profiles and decreased serum production of resistin, a well-established risk factor for both AD and atherosclerosis. Thus, the current study suggests and describes the therapeutic potential of β-OHB for the treatment of AD and atherosclerosis.
β-羟丁酸（β-OHB）已被证明具有抗炎活性。载脂蛋白-E（ApoE）与动脉粥样硬化和阿尔茨海默病（AD）密切相关。本研究旨在探讨β-OHB 对高脂肪饮食（HFD）喂养的载脂蛋白 E 缺陷（ApoE-deficient）小鼠大脑和主动脉的治疗作用。我们在 ApoE 缺陷小鼠中发现，β-OHB 可减轻脉络丛（ChP）中的脂质沉积，并减少黑质致密部的淀粉样斑块。我们还发现，β-OHB 治疗可减少 ChP 中 CD68 阳性的巨细胞浸润。β-OHB 治疗可改善 IgG 向大脑海马区的渗出。体外研究表明，β-OHB 可减轻氧化型低密度脂蛋白诱导的 ApoE 特异性差异表达的 ChP 炎症基因。β-OHB 治疗可减少主动脉斑块形成，而不影响血脂谱，并降低抵抗素的血清产生，抵抗素是 AD 和动脉粥样硬化的公认危险因素。因此，本研究提示并描述了β-OHB 治疗 AD 和动脉粥样硬化的治疗潜力。
