Submitted on July 31, 2008
Revised on January 26, 2009
Accepted on January 26, 2009
PET study of 11C-acetoacetate kinetics in rat brain during dietary treatments affecting ketosis
M'hamed Bentourkia1*, Sébastien Tremblay1, Fabien Pifferi1, Jacques Rousseau1, Roger Lecomte1, and Stephen Cunnane1
1 University of Sherbrooke
* To whom correspondence should be addressed. E-mail: mhamed.bentourkia{at}usherbrooke.ca.
Normally the brain's fuel is glucose but during fasting it increasingly relies on ketones (
-hydroxybutyrate, acetoacetate and acetone) produced in liver mitochondria from fatty acid -oxidation. Although moderately raised blood ketones produced on a very high fat ketogenic diet have important clinical effects on the brain, including reducing seizures, ketone metabolism by the brain is still poorly understood. The aim of the present work was to assess brain uptake of carbon-11 labeled acetoacetate (11C-acetoacetate) by positron emission tomography (PET) imaging in the intact, living rat. In order to vary plasma ketones, we used three dietary conditions: control diet (high carbohydrate; low plasma ketones), fat-rich ketogenic diet (raised plasma ketones), and 48 h fasting (raised plasma ketones). 11C-Acetoacetate metabolism was measured in brain, heart and tissue in the mouth area. Using 11C-acetoacetate and small animal PET imaging, we have noninvasively quantified a ~7-8 fold enhanced brain uptake of ketones on a ketogenic diet or during fasting. This opens up an opportunity to study brain ketone metabolism in humans.
