Regulation of kynurenine metabolism by a ketogenic diet

Svenja Heischmann, Lindsey B. Gano, Kevin Quinn, Li-Ping Liang, Jacek Klepacki, Uwe Christians, Nichole Reisdorph, Manisha Patel
2018 Journal of Lipid Research  
Ketogenic diets (KDs) are increasingly utilized as treatments for epilepsy, other neurological diseases, and cancer. Despite their long history in suppressing seizures, the distinct molecular mechanisms of action of KDs are still largely unknown. The goal of this study was to identify key metabolites and pathways altered in the hippocampus and plasma of rats fed a KD versus control diet (CD) either ad libitum or calorically restricted to 90% of the recommended intake. This was accomplished
more » ... s accomplished using a combination of targeted methods and untargeted MS-based metabolomics analyses. Various metabolites of and related to the tryptophan (TRP) degradation pathway, such as kynurenine (KYN), kynurenic acid as well as enzyme cofactors, showed significant changes between groups fed different diets and/or calorie amounts in plasma and/or the hippocampus. KYN was significantly downregulated in both matrices in animals of the CD-calorically restricted, KD-ad libitum, and KD-calorically restricted groups compared with the CD-ad libitum group. Our data suggest that the TRP degradation pathway is a key target of the KD.-Heischmann, S., L. B. Gano, K. Quinn, L-P. Liang, J. Klepacki, U. Christians, N. Reisdorph, and M. Patel. Regulation of kynurenine metabolism by a ketogenic diet. J. Lipid Res. 2018. 59: 958-966. Supplementary key words brain • diet effects/lipid metabolism • mass spectrometry • metabolomics • nutrition • epilepsy • kynurenine pathway • kynurenic acid • tryptophan • caloric restriction Ketogenic diets (KDs) are a popular therapy for refractory pediatric epilepsies (1, 2). The drastic reduction of carbohydrate intake diverts glucose utilization in favor of ketone bodies produced from fatty acids in the liver (2). In addition to provision of alternate fuels and induction of changes in the brain's energy reserve, acid-base balance, lipid profile, and levels of amino acid neurotransmitters are altered by KDs (1-3) . Epilepsy patients on this dietary
doi:10.1194/jlr.m079251 pmid:29605816 fatcat:7szigr3sfrastnweunaovlt5w4