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Ketone Metabolism in Brain Slices from Rats with Diet Induced Hyperketonemia¹

St. Luke's Hospital Center, Department of Medicine, Institute of Human Nutrition, Columbia University, College of Physicians and Surgeons, New York, New York 10025

The inducibility of ketone body utilization in brain was investigated in vitro in rats fed for 21 days three diets of varying ketogenicity: a nonketogenic low-fat diet (St. diet), a moderately ketogenic high corn oil diet (LCT diet), and a highly ketogenic high medium chain triglyceride diet (MCT diet). The protein:energy ratio was the same for all the diets. Total blood ketone body concentrations were 0.19 mM, 0.35 mM, and 0.94 mM in St., LCT, and MCT diets respectively. In brain slices the uptake (50 µmoles/g/2 hours) and metabolism of [U-¹⁴C]glucose (40% in lactate, 30% in CO₂ and less than 2% into lipids and glycogen) were independent of the diets. Addition of 10 mM cold DL ß-hydroxybutyrate decreased by 30% glucose uptake and by 50% the labelling of CO₂ and fatty acids, while increasing lactate release, regardless of the nature of the diet. The uptake (20 µmoles/g/2 hours) and conversion of ß-hydroxy [3-¹⁴C]butyrate into CO₂ (40%) and lipids (<1%) were independent of the diets. Addition of 10 mM cold glucose increased by 40% ß-hydroxybutyrate uptake and by 100% the labelling of CO₂ and fatty acids in brain slices, irrespective of the diet. Consistently, ß-hydroxybutyrate dehyrogenase enzyme activity had the same level in all brains. The data suggest that dietary-induced hyperketonemia, like starvation-induced hyperketonemia, influences brain metabolism through substrate concentration without apparent long-term inductive effects.

KEY WORDS: • medium chain triglyceride • long chain triglyceride • high-fat diet • glucose uptake and utilization • ß-hydroxbutyrate dehydrogenase • glucose sparing effect of ketones

¹ This study was supported by grant (AM-17191) from the National Institutes of Health, the United States Public Health Service.

² Marcelle Lavau is Chargee de Recherces de l'Institut National de la Sante et de la Recherche Medicale (INSERM), Paris.

³ Address for reprints: Department of Medicine, St. Luke's Hospital Center, Amsterdam Avenue and 114th St., New York, New York 10025.

Manuscript received 6 June 1977.