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  • 标题:Ketone production by ketogenic diet and by intermittent fasting has different effects on the gut microbiota and disease progression in an Alzheimer’s disease rat model
  • 本地全文:下载
  • 作者:Sunmin Park ; Ting Zhang ; Xuangao Wu
  • 期刊名称:Journal of Clinical Biochemistry and Nutrition
  • 印刷版ISSN:0912-0009
  • 电子版ISSN:1880-5086
  • 出版年度:2020
  • 卷号:67
  • 期号:2
  • 页码:188-198
  • DOI:10.3164/jcbn.19-87
  • 出版社:The Society for Free Radical Research Japan
  • 摘要:

    The benefits of ketone production regimens remain controversial. Here, we hypothesized that the ketone-producing regimens modulated cognitive impairment, glucose metabolism, and inflammation while altering the gut microbiome. The hypothesis and the mechanism were explored in amyloid-β infused rats. Rats that received an amyloid-β(25–35) infusion into the hippocampus had either ketogenic diet (AD-KD), intermittent fasting (AD-IMF), 30 energy percent fat diet (AD-CON), or high carbohydrate (starch) diet (AD-CHO) for 8 weeks. AD-IMF and AD-CHO, but not AD-KD, lowered the hippocampal amyloid-β deposition compared to the AD-CON despite serum ketone concentrations being elevated in both AD-KD and AD-IMF. AD-IMF and AD-CHO, but not AD-KD, improved memory function in passive avoidance, Y maze, and water maze tests compared to the AD-CON. Hippocampal insulin signaling (pAkt→pGSK-3β) was potentiated and pTau was attenuated in AD-IMF and AD-CHO much more than AD-CON. AD-IMF and AD-CON had similar glucose tolerance results during OGTT, but AD-KD and AD-IMF exhibited glucose intolerance. AD-KD exacerbated gut dysbiosis by increasing Proteobacteria , and AD-CHO improved it by elevating Bacteriodetes . In conclusion, ketone production itself might not improve memory function, insulin resistance, neuroinflammation or the gut microbiome when induced by ketone-producing remedies. Intermittent fasting and a high carbohydrate diet containing high starch may be beneficial for people with dementia.

  • 关键词:ketone;amyloid-β;hippocampus;insulin signaling;gut microbiome
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