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β-hydroxybutyrate Impedes the Progression of Alzheimer’s Disease and Atherosclerosis in ApoE-Deficient Mice

1
Department of Biochemistry, School of Medicine, Keimyung University, Daegu 42601, Korea
2
Clinical Medicine Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2020, 12(2), 471; https://doi.org/10.3390/nu12020471
Received: 1 February 2020 / Revised: 11 February 2020 / Accepted: 12 February 2020 / Published: 13 February 2020
(This article belongs to the Section Micronutrients and Human Health)
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.
Keywords: Alzheimer’s disease; β-hydroxybutyrate; atherosclerosis; choroid plexus; apolipoprotein-E Alzheimer’s disease; β-hydroxybutyrate; atherosclerosis; choroid plexus; apolipoprotein-E
MDPI and ACS Style

Krishnan, M.; Hwang, J.S.; Kim, M.; Kim, Y.J.; Seo, J.H.; Jung, J.; Ha, E. β-hydroxybutyrate Impedes the Progression of Alzheimer’s Disease and Atherosclerosis in ApoE-Deficient Mice. Nutrients 2020, 12, 471.

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