生酮饮食
酮体
酮症
内科学
内分泌学
生物
医学
新陈代谢
癫痫
糖尿病
神经科学
作者
Ester Aso,Jana Semakova,Laura Joda,Vladislav Semak,Lyda Halbaut,Ana Cristina Calpena,Carmen Escolano,José C. Perales,Isidro Ferrer
标识
DOI:10.2174/15672050112099990128
摘要
Diets containing a high proportion of fat with respect to protein plus carbohydrates are capable of inducing ketone body production in the liver, which provides an energetic alternative to glucose. Some ketogenic diets have been tested as therapeutic strategies for treating metabolic disorders related to a deficiency in glucose-driven ATP generation. However, ketone bodies are not capable of providing extra tricarboxylic acid cycle intermediates, limiting the anabolic capacity of the cell. Therefore, it is reasonable to hypothesize that supplementing a ketogenic diet with anaplerotic compounds such as triheptanoin may improve ketogenic diet effectiveness. The present study tests this hypothesis in APP/PS1 (APPswe/PS1dE9) transgenic mice, used as a model of familial Alzheimer’s disease because impaired energy supply to neurons has been linked to this neurodegenerative process. Triheptanoin supplementation to a ketogenic diet for three months and starting at the age of three months reduces the memory impairment of APP/PS1 mice at the age of 6 months. The Aβ production and deposition were not significantly altered by the ketogenic diet, supplemented or not by triheptanoin. However, mice fed with triheptanoin-rich ketogenic diet have shown decreased astroglial response in the vicinity of Aβ plaques and decreased expression of the pro-inflammatory cytokine interferon-γ in astrocytes. These findings correlate with transcriptional up-regulation of the ROS detoxifying mechanisms Sirt1 and Pparg, thus linking triheptanoin with improved mitochondrial status. Present findings support the concept that ketogenic diets supplemented with anaplerotic compounds can be considered potential therapeutic strategies at early stages of Alzheimer’s disease. Keywords: Alzheimer’s disease, anaplerotic diet, APP/PS1 transgenic mice, ketone bodies, mitochondria, triheptanoin
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