A Ketone Ester Diet Increases Brain Malonyl-CoA and Uncoupling Proteins 4 and 5 while Decreasing Food Intake in the Normal Wistar Rat |
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| Authors: | Yoshihiro Kashiwaya Robert Pawlosky William Markis M Todd King Christian Bergman Shireesh Srivastava Andrew Murray Kieran Clarke Richard L Veech |
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| Institution: | From the ‡Laboratory of Metabolic Control, NIAAA, National Institutes of Health, Rockville, Maryland 20852-9047.;the §Department of Physiology, Development & Neuroscience, University of Cambridge, Cambridge CB2 3EG, United Kingdom, and ;the ¶Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom |
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| Abstract: | Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial NAD+]/NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain l-glutamate by 15–20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain. |
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| Keywords: | Acetoacetate Beta-hydroxybutyrate Brain Metabolism Ketone Bodies Ketone Body Metabolism Malonyl-CoA Uncoupling Protein |
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