The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders.
This review outlines the molecular sensors that reprogram cellular metabolism in response to the ketogenic diet (KD). Special emphasis is placed on the fasting-, fatty acid- and drug-activated transcription factor, peroxisome proliferator-activated receptor alpha (PPARalpha). The KD causes a switch to ketogenesis that is coordinated with an array of changes in cellular lipid, amino acid, carbohydrate and inflammatory pathways. The role of both liver and brain PPARalpha in mediating such changes will be examined, with special reference to the anti-epileptic effects not only of the KD but a range of synthetic anti-epileptic drugs such as valproate. Finally, the implications of the KD and activated brain PPARalpha will be discussed in the context of their potential involvement in a range of disorders of neuro-degeneration and neuro-inflammation.
Cullingford
Tim E
TE
Faculty of Pharmaceutical Sciences, Department of Clinical and Molecular Pharmacokinetics/Pharmacodynamics, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. teculling@hotmail.com
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004032:Diet; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000378:metabolism; D007659:Ketones / Q000378:metabolism*; D009422:Nervous System Diseases / Q000378:metabolism* / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D005227:Fatty Acids; D007659:Ketones; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D006904:Hydroxymethylglutaryl-CoA Synthase