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.

Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2013
Total Cost
$1,308,527
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
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Zip Code
Murray, Andrew J; Knight, Nicholas S; Cole, Mark A et al. (2016) Novel ketone diet enhances physical and cognitive performance. FASEB J :
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
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Srivastava, Shireesh; Baxa, Ulrich; Niu, Gang et al. (2013) A ketogenic diet increases brown adipose tissue mitochondrial proteins and UCP1 levels in mice. IUBMB Life 65:58-66
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