Ketone bodies serve as important precursors of brain lipids in the developing rat

Ketone bodies are readily oxidized for energy by extrahepatic tissues. Since oxidation of ketone bodies produces acetyl coenzyme A (AcCoA), and hence could be an important source of immediate precursors for fatty acid synthesis, we investigated, in whole‐brain homogenates of developing rats, the preferential utilization of [3‐14C]acetoacetate (AcAc), [3‐14C]β‐hydroxybutyrate (β‐OHB), and [U‐14C]glucose for production of CO2 and lipids, including phospholipids, glycerides, cholesterol, and free fatty acids. Throughout the postnatal period, the rate of AcAc oxidation was 2–3 and 2–6 times the rate for β‐OHB and glucose, respectively. The eynthesis of lipids from AcAc was 7‐ to 11‐fold higher than from glucose. The brain's capacity for lipid synthesis from β‐OHB was similar to that from AcAc during the first 8 days of life; however, during the next 10 days, the synthesis of lipids from β‐OHB decreased to 60% of AcAc‐dependent synthesis. The high rate of lipid synthesis from ketone bodies was accompanied by increased activities of cytoplasmic acetoacetyl CoA synthetase and acetoacetyl CoA thiolase in the developing brain. During the entire postnatal development, the proportion of radioactivity claimed by lipids vs. CO2 from [3‐14C]AcAc was 44–62% vs. 38–56%; from [3‐14C]β‐OHB, 50–81% vs. 19–50%; and from [U‐14C]glucose, 14–43% vs. 57–86%. Phospholipids accounted for more than two‐thirds of total lipids synthesized from either ketone bodies or glucose, while diglycerides plus cholesterol and free fatty acids accounted for most of the remainder. Addition of glucose to the incubation medium did not alter lipid production from AcAc throughout the suckling period, but moderately depressed energy production in the brain of 16‐ to 20‐day‐old rats. It is clear that in cell‐free preparations from the brain of developing rats, ketone bodies are preferred over glucose as precursors for both energy and lipids, mainly phospholipids. These results suggest that ketone bodies are important for the growth and development of the brain.