3‐Hydroxybutyrate regulates energy metabolism and induces BDNF expression in cerebral cortical neurons

作者：Krisztina Marosi, Sang Woo Kim, Keelin Moehl, Morten Scheibye‐Knudsen, Aiwu Cheng, Roy G. Cutler, Simonetta Camandola, Mark P. Mattson · 发表于：Journal of Neurochemistry · 年份：2016 · DOI：10.1111/jnc.13868 · 被引用次数：247 · 研究领域：Diet and metabolism studies、Adipose Tissue and Metabolism、Biochemical effects in animals

Abstract During fasting and vigorous exercise, a shift of brain cell energy substrate utilization from glucose to the ketone 3‐hydroxybutyrate (3 OHB ) occurs. Studies have shown that 3 OHB can protect neurons against excitotoxicity and oxidative stress, but the underlying mechanisms remain unclear. Neurons maintained in the presence of 3 OHB exhibited increased oxygen consumption and ATP production, and an elevated NAD + / NADH ratio. We found that 3 OHB metabolism increases mitochondrial respiration which drives changes in expression of brain‐derived neurotrophic factor ( BDNF ) in cultured cerebral cortical neurons. The mechanism by which 3 OHB induces Bdnf gene expression involves generation of reactive oxygen species, activation of the transcription factor NF ‐κB, and activity of the histone acetyltransferase p300/ EP 300. Because BDNF plays important roles in synaptic plasticity and neuronal stress resistance, our findings suggest cellular signaling mechanisms by which 3 OHB may mediate adaptive responses of neurons to fasting, exercise, and ketogenic diets. image