Abstract
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.
Highlights
World Alzheimer Report 2018 states that 50 million people worldwide are living with dementia, and this number will more than triple to 152 million by 2050
Our data in the current study indicate that β-OHB delays the progression of Alzheimer’s disease (AD) by inhibiting lipid accumulation and inflammatory reactions in the brain, and of atherosclerosis by decreasing plaque formation in the aorta
We found that β-OHB ameliorated high-fat diet (HFD)-induced
Summary
World Alzheimer Report 2018 states that 50 million people worldwide are living with dementia, and this number will more than triple to 152 million by 2050. The total estimated worldwide cost of dementia in 2018 is one trillion US dollars, which is expected to rise to two trillion US dollars by. The understanding of the neurobiology and pathogenesis of Alzheimer’s disease (AD), the most common form of dementia, has recently been greatly increased, no curative, but only a few symptomatic treatments, are currently available. Human apolipoprotein-E (ApoE) is a polymorphic multifunctional protein with isoforms of ApoE2, ApoE3, and ApoE4, and is strongly implicated in two major inflammatory diseases, AD and atherosclerosis. Atherosclerosis, characterized by lipid plaque formation in the aorta, is the leading cause of cardiovascular disease [4]. Action mechanisms of Nutrients 2020, 12, 471; doi:10.3390/nu12020471 www.mdpi.com/journal/nutrients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
