The metabolic state of the brain can greatly impact neurologic function. Evidence of this includes the therapeutic benefit of a ketogenic diet in neurologic diseases, including epilepsy. However, brain lipid bioenergetics remain largely uncharacterized. The existence, capacity, and relevance of mitochondrial fatty acid β-oxidation (FAO) in the brain are highly controversial, with few genetic tools available to evaluate the question. We have provided evidence for the capacity of brain FAO using a pan-brain-specific conditional knockout (KO) mouse incapable of FAO due to the loss of carnitine palmitoyltransferase 2, the product of an obligate gene for FAO (CPT2B-/-). Loss of central nervous system (CNS) FAO did not result in gross neuroanatomical changes or systemic differences in metabolism. Loss of CPT2 in the brain did not result in robustly impaired behavior. We demonstrate by unbiased and targeted metabolomics that the mammalian brain oxidizes a substantial quantity of long-chain fatty acids in vitro and in vivo Loss of CNS FAO results in robust accumulation of long-chain acylcarnitines in the brain, suggesting that the mammalian brain mobilizes fatty acids for their oxidation, irrespective of diet or metabolic state. Together, these data demonstrate that the mammalian brain oxidizes fatty acids under normal circumstances with little influence from or on peripheral tissues.

中文翻译：

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确定哺乳动物神经系统中脂肪酸氧化的生物能能力。

大脑的代谢状态可以极大地影响神经功能。这方面的证据包括生酮饮食对神经系统疾病（包括癫痫）的治疗益处。然而，脑脂质生物能学在很大程度上仍然未知。大脑中线粒体脂肪酸β-氧化（FAO）的存在、能力和相关性存在很大争议，很少有遗传工具可以评估这个问题。我们使用泛脑特异性条件敲除（KO）小鼠提供了大脑FAO能力的证据，该小鼠由于肉碱棕榈酰转移酶2（FAO专性基因（CPT2B-/-）的产物）的缺失而无法进行FAO。中枢神经系统（CNS）的丧失FAO不会导致严重的神经解剖学变化或代谢的系统性差异。大脑中 CPT2 的缺失并不会导致行为严重受损。我们通过公正和有针对性的代谢组学证明，哺乳动物大脑在体外和体内氧化大量的长链脂肪酸。中枢神经系统FAO的损失导致长链酰基肉碱在大脑中大量积累，这表明哺乳动物大脑动员脂肪酸的氧化作用，无论饮食或代谢状态如何。总之，这些数据表明，哺乳动物大脑在正常情况下氧化脂肪酸，而周围组织的影响很小。