Partition of ketone bodies into cholesterol and fatty acids in vivo in different brain regions of developing rats

Abstract

The proportions of labeled ketone bodies and glucose incorporated into cholesterol and fatty acids in different regions of the brain in developing rats were compared. In cerebrums of 15- and 18-day-old rats, the ratios of dpm cholesterol/dpm fatty acids incorporated from [3-¹⁴C] acetoacetate and [3-¹⁴C] β-hydroxybutyrate ranged from 0.4 to 0.7, or 50 to 100% higher than values obtained with [U-¹⁴C] glucose. Much higher ratios were obtained with younger animals: from 1 to 12 days of life, the values ranged from 1.0 to 1.3 with [3-¹⁴C] β-hydroxybutyrate as substrate, and, from 1 to 5 days, with [3-¹⁴C] acetoacetate, they were 1.0 or greater. During the first 12 days of life, the ratios resulting from administration of [U-¹⁴C] glucose were 0.4–0.7. Clearly, a greater proportion of acetoacetate and β-hydroxybutyrate was incorporated into cholesterol during the first week of life than the remaining suckling period. Like cerebrum, other brain regions (i.e., cerebellum, midbrain, brain stem and thalamus) yielded higher ratios of dpm cholesterol/dpm fatty acids from [3-¹⁴C] β-hydroxybutyrate during the first 12 days of life than on day 17. Brain stem was the most active region for lipid synthesis, and had the highest dpm cholesterol/dpm fatty acid ratio. Since active synthesis of cholesterol from ketone bodies during the early postnatal period coincides with a period of rapid brain growth, the results indicate that ketone bodies are more important early in the suckling period as sources of cholesterol for brain growth.