Experimental and clinical data support the neuroprotective properties of the ketogenic diet and ketone bodies, but there is still a lot to discover to comprehensively understand the underlying mechanisms. Autophagy is a key mechanism for maintaining cell homeostasis, and therefore its proper function is necessary for preventing accelerated brain aging and neurodegeneration. Due to many potential interconnections, it is possible that the stimulation of autophagy may be one of the mediators of the neuroprotection afforded by the ketogenic diet. Recent studies point to possible interconnections between ketone body metabolism and autophagy. It has been shown that autophagy is essential for hepatic and renal ketogenesis in starvation. On the other hand, exogenous ketone bodies modulate autophagy both in vitro and in vivo. Many regional differences occur between brain structures which concern i.e., metabolic responses and autophagy dynamics. The aim of the present study was to evaluate the influence of the ketogenic diet on autophagic markers and the ketone body utilizing and transporting proteins in the hippocampus and frontal cortex. C57BL/6N male mice were fed with two ketogenic chows composed of fat of either animal or plant origins for 4 weeks. Markers of autophagosome formation as well as proteins associated with ketolysis (BDH1-3-hydroxybutyrate dehydrogenase 1, SCOT/OXCT1-succinyl CoA:3-oxoacid CoA transferase), ketone transport (MCT1-monocarboxylate transporter 1) and ketogenesis (HMGCL, HMGCS2) were measured. The hippocampus showed a robust response to nutritional ketosis in both changes in the markers of autophagy as well as the levels of ketone body utilizing and transporting proteins, which was also accompanied by increased concentrations of ketone bodies in this brain structure, while subtle changes were observed in the frontal cortex. The magnitude of the effects was dependent on the type of ketogenic diet used, suggesting that plant fats may exert a more profound effect on the orchestrated upregulation of autophagy and ketone body metabolism markers. The study provides a foundation for a deeper understanding of the possible interconnections between autophagy and the neuroprotective efficacy of nutritional ketosis.

中文翻译：

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海马和脑皮质自噬和酮体代谢对生酮饮食的差异反应。

实验和临床数据支持生酮饮食和酮体的神经保护特性，但要全面了解其潜在机制还有很多需要发现。自噬是维持细胞稳态的关键机制，因此其适当的功能对于防止加速脑老化和神经变性是必要的。由于许多潜在的相互联系，自噬的刺激可能是生酮饮食提供的神经保护的介质之一。最近的研究指出酮体代谢和自噬之间可能存在联系。已经表明，自噬对于饥饿时肝脏和肾脏的生酮是必不可少的。另一方面，外源性酮体在体外和体内调节自噬。在涉及代谢反应和自噬动力学的大脑结构之间存在许多区域差异。本研究的目的是评估生酮饮食对自噬标志物和酮体利用和运输海马和额叶皮层蛋白质的影响。C57BL/6N 雄性小鼠用两种由动物或植物来源的脂肪组成的生酮食物喂养 4 周。自噬体形成的标志物以及与酮解相关的蛋白质（BDH1-3-羟基丁酸脱氢酶 1、SCOT/OXCT1-琥珀酰辅酶 A：3-含氧酸辅酶 A 转移酶）、酮转运（MCT1-单羧酸转运蛋白 1）和生酮（HMGCL、HMGCS2）被测量。海马体在自噬标志物的变化以及酮体利用和运输蛋白质的水平上都表现出对营养酮症的强烈反应，这也伴随着该大脑结构中酮体浓度的增加，同时观察到了细微的变化在额叶皮层。影响的程度取决于所使用的生酮饮食的类型，这表明植物脂肪可能对自噬和酮体代谢标志物的协调上调产生更深远的影响。该研究为更深入地了解自噬与营养酮症的神经保护功效之间可能存在的联系奠定了基础。而在额叶皮层中观察到细微的变化。影响的程度取决于所使用的生酮饮食的类型，这表明植物脂肪可能对自噬和酮体代谢标志物的协调上调产生更深远的影响。该研究为更深入地了解自噬与营养酮症的神经保护功效之间可能存在的联系奠定了基础。而在额叶皮层中观察到细微的变化。影响的程度取决于所使用的生酮饮食的类型，这表明植物脂肪可能对自噬和酮体代谢标志物的协调上调产生更深远的影响。该研究为更深入地了解自噬与营养酮症的神经保护功效之间可能存在的联系奠定了基础。