Abstracts

Animals fed high-fat (ketogenic) diets use ketone bodies to supplement glucose for cerebral metabolism. Quantitative data are available for humans but no descriptions of glucose and beta-hydroxybutyrate extraction from cerebral circulation have been reported for rats, though metabolic studies have shown that rat brain appears to be less dependent upon ketone bodies than does human brain during consumption of ketogenic diets.
Male Sprague-Dawley rats were placed on a high-fat diet (BioServe F3666) and age- and weight-matched cohorts were maintained on a standard rodent chow (Purina 5001) for at least 20 days. At the end of this time, rats were anesthetized with ketamine:xylazine (75 mg/kg:25 mg/kg, resp.) and the right jugular and left carotid were exposed. Blood was first taken from the jugular vein using a 27-gauge needle. Subsequently, blood was obtained from the carotid artery or, if the artery were ruptured, from the pool of blood that rapidly formed. Glucose and BHB concentrations were determined from aliquots of single samples taken from each source. Glucose levels were determined using Precision Xtra strips (Abbott) and BHB was measured using Stat-Site cards (GDS, now Stanbio).
Glucose concentrations in jugular blood were lower than those in carotid blood taken from rats fed either diet. There was no detectable difference between jugular and carotid blood BHB concentrations in rats fed the normal diet. Most surprisingly, rats fed the ketogenic diet showed higher concentrations of BHB in jugular blood than in carotid blood (P [lt] 0.001, Mann-Whitney U test).
Unless a fraction of the excess BHB in jugular blood is from non-brain sources, this finding suggests that rat brain is synthesizing BHB, a finding consistent with a report (Cullingford et al., 2002, Epilepsy Res. 49:99-107) showing elevation of brain and liver mRNA for a key ketogenic enzyme (mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase) in rats fed a high-fat diet, and with reports suggesting that rat brain extracts proportionately less BHB from the circulation than does human brain. It is unclear whether this apparent export of BHB by the brain is an artifact of anesthesia or surgery or, if physiological, what it might imply about CNS metabolism in rodents fed ketogenic diets and the relationship to reduction in seizure threshold seen in animals fed such diets.
[Supported by: Department of Biology, Georgetown University]