A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat.
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.
Laboratory of Metabolic Control, NIAAA, National Institutes of Health, Rockville, Maryland 20852-9047, USA.
Yoshihiro
Y
Kashiwaya
Robert
R
Pawlosky
William
W
Markis
M Todd
MT
King
Christian
C
Bergman
Shireesh
S
Srivastava
Andrew
A
Murray
Kieran
K
Clarke
Richard L
RL
Veech
D020155:3-Hydroxybutyric Acid; D000818:Animals; D001923:Brain Chemistry; D002072:Butylene Glycols; D004032:Diet; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism; D004952:Esters / Q000008:administration & dosage / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D018698:Glutamic Acid / Q000187:drug effects; D007473:Ion Channels / Q000096:biosynthesis / Q000187:drug effects*; D007657:Ketone Bodies / Q000378:metabolism; D008297:Male; D008316:Malonyl Coenzyme A / Q000097:blood / Q000187:drug effects*; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000187:drug effects*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000187:drug effects*; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000187:drug effects*; D000073878:Palm Oil; D010938:Plant Oils / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000187:drug effects
D002072:Butylene Glycols; D004952:Esters; D005227:Fatty Acids; D007473:Ion Channels; D007657:Ketone Bodies; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; D010938:Plant Oils; C492125:Slc25a14 protein, rat; C494853:Slc25a27 protein, rat; D018698:Glutamic Acid; D008316:Malonyl Coenzyme A; D005680:gamma-Aminobutyric Acid; D000073878:Palm Oil; D020155:3-Hydroxybutyric Acid