PMID- 37967727 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20231229 IS - 1872-8006 (Electronic) IS - 0304-4165 (Linking) VI - 1868 IP - 1 DP - 2024 Jan TI - 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. PG - 130521 LID - S0304-4165(23)00219-2 [pii] LID - 10.1016/j.bbagen.2023.130521 [doi] AB - 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 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 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, 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. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Demianchuk, Oleh AU - Demianchuk O AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine. FAU - Vatashchuk, Myroslava AU - Vatashchuk M AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine. FAU - Gospodaryov, Dmytro AU - Gospodaryov D AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine. Electronic address: dmytro.gospodaryov@pnu.edu.ua. FAU - Hurza, Viktoria AU - Hurza V AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine. FAU - Ivanochko, Marian AU - Ivanochko M AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine. FAU - Derkachov, Vitalii AU - Derkachov V AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine. FAU - Berezovskyi, Vladyslav AU - Berezovskyi V AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine. FAU - Lushchak, Oleh AU - Lushchak O AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine; Research and Development University, 13a Shota Rustaveli Str., Ivano-Frankivsk, 76018, Ukraine. FAU - Storey, Kenneth B AU - Storey KB AD - Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada. FAU - Bayliak, Maria AU - Bayliak M AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine. Electronic address: maria.bayliak@pnu.edu.ua. FAU - Lushchak, Volodymyr I AU - Lushchak VI AD - Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine; Research and Development University, 13a Shota Rustaveli Str., Ivano-Frankivsk, 76018, Ukraine. Electronic address: volodymyr.lushchak@pnu.edu.ua. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231113 PL - Netherlands TA - Biochim Biophys Acta Gen Subj JT - Biochimica et biophysica acta. General subjects JID - 101731726 RN - 0 (Ketoglutaric Acids) RN - 30237-26-4 (Fructose) SB - IM MH - Mice MH - Animals MH - *Ketoglutaric Acids MH - *Fructose MH - Diet, High-Fat/adverse effects MH - Oxidative Stress MH - Energy Metabolism OTO - NOTNLM OT - Behavior OT - Brain OT - Glycolysis OT - High caloric diet OT - Mitochondria, oxidative stress OT - alpha-Ketoglutarate COIS- Declaration of Competing Interest The authors declare that they have no conflict of interest. EDAT- 2023/11/16 00:42 MHDA- 2023/12/17 09:43 CRDT- 2023/11/15 19:23 PHST- 2023/08/28 00:00 [received] PHST- 2023/10/19 00:00 [revised] PHST- 2023/11/09 00:00 [accepted] PHST- 2023/12/17 09:43 [medline] PHST- 2023/11/16 00:42 [pubmed] PHST- 2023/11/15 19:23 [entrez] AID - S0304-4165(23)00219-2 [pii] AID - 10.1016/j.bbagen.2023.130521 [doi] PST - ppublish SO - Biochim Biophys Acta Gen Subj. 2024 Jan;1868(1):130521. doi: 10.1016/j.bbagen.2023.130521. Epub 2023 Nov 13.