Background

High caloric diets with high amounts of fats and sweeteners such as fructose may predispose organisms to neurodegenerative diseases.

Methods

This study aimed to examine the effects of a high-fat high-fructose diet (HFFD) on the behavior of mice, energy metabolism, and markers of oxidative stress in murine cerebral cortex. Dietary α-ketoglutarate (AKG) was chosen as a treatment which could modulate the putative effects of HFFD.

Results

We found that HFFD stimulated locomotion and defecation in mice, whereas an AKG-supplemented diet had a proclivity to promote anxiety-like behavior. HFFD stimulated lipid peroxidation, and in turn, the AKG-supplemented diet led to a higher ratio of reduced to oxidized glutathione, higher activity of NAD(P)H:quinone oxidoreductase 1, and higher mRNA levels of UDP-glucose 6-dehydrogenase and transcription factor EB. Both diets separately, but not in combination, led to a decrease in the activities of glutathione peroxidase, glutathione S-transferase, and phosphofructokinase. All experimental diets resulted in lower levels of transcripts of genes encoding pyruvate dehydrogenase kinase 4 (PDK4), glycine N-methyl transferase, and peroxisome proliferator receptor γ co-activator 1.

Conclusions

Our results show that diet supplemented with AKG resulted in effects similar to those of HFFD on the cerebral cortex, but elicited substantial differences between these two diets with respect to behavior, glutathione-dependent detoxification, and processes related to autophagy.

General significance

Our study provides insight into the metabolic effects of HFFD alone and in combination with alpha-ketoglutarate in the mouse brain.

中文翻译：

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高脂高果糖饮食和α-酮戊二酸影响小鼠行为，并伴有大脑皮层氧化应激反应和能量代谢的变化

背景

含有大量脂肪和果糖等甜味剂的高热量饮食可能会使生物体容易患神经退行性疾病。

方法

本研究旨在探讨高脂高果糖饮食 (HFFD) 对小鼠行为、能量代谢和小鼠大脑皮层氧化应激标志物的影响。选择饮食 α-酮戊二酸 (AKG) 作为可以调节 HFFD 假定效果的治疗方法。

结果

我们发现 HFFD 刺激小鼠的运动和排便，而补充 AKG 的饮食则倾向于促进类似焦虑的行为。HFFD 刺激脂质过氧化，反过来，补充 AKG 的饮食导致还原型谷胱甘肽与氧化型谷胱甘肽的比例更高、NAD( P )H:醌氧化还原酶1 活性更高、UDP-葡萄糖 6-脱氢酶和 UDP-葡萄糖 6-脱氢酶 mRNA 水平更高转录因子EB。两种饮食单独（但不组合）导致谷胱甘肽过氧化物酶、谷胱甘肽S-转移酶和磷酸果糖激酶的活性降低。所有实验饮食均导致编码丙酮酸脱氢酶激酶 4 (PDK4)、甘氨酸N-甲基转移酶和过氧化物酶体增殖物受体 γ 共激活剂 1 的基因转录物水平较低。

结论

我们的结果表明，补充 AKG 的饮食对大脑皮层产生的影响与 HFFD 相似，但在行为、谷胱甘肽依赖性解毒和自噬相关过程方面，这两种饮食之间存在显着差异。

一般意义

我们的研究深入了解了 HFFD 单独使用以及与 α-酮戊二酸联合使用对小鼠大脑的代谢影响。