Journal
JOURNAL OF LIPID RESEARCH
Volume 59, Issue 6, Pages 958-966Publisher
ELSEVIER
DOI: 10.1194/jlr.M079251
Keywords
brain; diet effects/lipid metabolism; mass spectrometry; metabolomics; nutrition; epilepsy; kynurenine path-way; kynurenic acid; tryptophan; caloric restriction
Categories
Funding
- Citizens United for Research in Epilepsy (Infantile Spasms Initiative)
- National Institutes of Health [RO1NS039587, R01NS086423S1]
- American Epilepsy Society
- National Institutes of Health National Research Service Award [F32NS090808]
- Colorado Clinical and Translational Sciences Institute [UL-1-RRO25780]
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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 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.
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