High-fat high-fructose diet and alpha-ketoglutarate affect mouse behavior that is accompanied by changes in oxidative stress response and energy metabolism in the cerebral cortex

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 alpha-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 AKGsupplemented 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 gamma 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, glutathionedependent 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.

Automated summary

This study investigated the effects of a high-fat high-fructose diet (HFFD) on the behavior, energy metabolism, and oxidative stress markers in the cerebral cortex of mice. The results showed that HFFD stimulated locomotion and defecation, while an AKG-supplemented diet had a tendency to promote anxiety-like behavior. Additionally, there were significant differences in glutathione-dependent detoxification and processes related to autophagy between the two diets.