We have developed a system of analysis of metabolites using CE and GC mass spectroscopy suitable for measurement of small tissue samples. Metabolites in defined pathways are analyzed and the data viewed in terms of the variations in the major energetic parameters of redox and phosphorylation states. We have examined the effects of feeding ketone ester diets upon brain intermediary metabolism. We found that feeding ketone bodies increased the energy of ATP hydrolysis in brain, which may have significance in increasing the extent of ionic gradients in nerve cells, which is likely to account in part for the ability of ketosis to decrease epileptic episodes in some cases of drug resistant epilepsy. Additionally feeding ketones increased brain malonyl CoA, which may make this approach useful in the treatment of obesity and related diseases such as type II diabetes. A practical dietary regime has been developed which may be of clinical use in the treatment of very common diseases affecting the state of public health in the United States and elsewhere in the developed world.

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National Institute on Alcohol Abuse and Alcoholism
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Pawlosky, Robert J; Kemper, Martin F; Kashiwaya, Yoshihero et al. (2017) Effects of a dietary ketone ester on hippocampal glycolytic and tricarboxylic acid cycle intermediates and amino acids in a 3xTgAD mouse model of Alzheimer's disease. J Neurochem 141:195-207
Veech, Richard L; Bradshaw, Patrick C; Clarke, Kieran et al. (2017) Ketone bodies mimic the life span extending properties of caloric restriction. IUBMB Life 69:305-314
Murray, Andrew J; Knight, Nicholas S; Cole, Mark A et al. (2016) Novel ketone diet enhances physical and cognitive performance. FASEB J :
Cox, Pete J; Kirk, Tom; Ashmore, Tom et al. (2016) Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab 24:256-68
Sato, Shogo; Jung, Hunmin; Nakagawa, Tsutomu et al. (2016) Metabolite Regulation of Nuclear Localization of Carbohydrate-response Element-binding Protein (ChREBP): ROLE OF AMP AS AN ALLOSTERIC INHIBITOR. J Biol Chem 291:10515-27
Shivva, Vittal; Cox, Pete J; Clarke, Kieran et al. (2016) The Population Pharmacokinetics of D-?-hydroxybutyrate Following Administration of (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate. AAPS J 18:678-88
Newport, Mary T; VanItallie, Theodore B; Kashiwaya, Yoshihiro et al. (2015) A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease. Alzheimers Dement 11:99-103
Kemper, Martin F; Srivastava, Shireesh; Todd King, M et al. (2015) An Ester of ?-Hydroxybutyrate Regulates Cholesterol Biosynthesis in Rats and a Cholesterol Biomarker in Humans. Lipids 50:1185-93
Lendvai, Nikoletta; Pawlosky, Robert; Bullova, Petra et al. (2014) Succinate-to-fumarate ratio as a new metabolic marker to detect the presence of SDHB/D-related paraganglioma: initial experimental and ex vivo findings. Endocrinology 155:27-32
Veech, Richard L (2014) Ketone ester effects on metabolism and transcription. J Lipid Res 55:2004-6

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