Changes in Lipogenic Capacity and Activities of Ketolytic and Lipogenic Enzymes in Brain Regions of Developing Rats

Oxidation of ketone bodies (KBs) generates acetyl coenzyme A (AcCoA), which can be further incorporated into fatty acid. We have determined the rates of lipogenesis from ketone bodies in developing rats and their relation to the activities of enzymes involved in the production of cytoplasmic AcCoA via different pathways in brain regions. In the cerebrum (Cbr), rates of fatty acid synthesis from [3-14C]acetoacetate ([3-14C]AcAc) were high during the early postnatal period but decreased rapidly thereafter until weaning. Although similar developmental patterns of synthesis characterized the cerebellum (Cbl), midbrain (Mb), brain stem (Bs), and thalamus (Th), maximal rates were highest in the Cbr and lowest in the Th. In all regions, synthetic rates were higher throughout the entire suckling period than in adulthood. There were not appreciable differences in synthetic rates among brain regions of adult rats. The developmental changes in rates AcAc incorporation into fatty acids were closely related to AcAcCoA synthetase activity, but not to activities of ATP-citrate lyase or AcCoA synthetase. During the early postnatal stage enhanced rates of lipogenesis were accompanied by increased activities of AcAcCoA synthetase in all regions, with the highest activity occurring in the Cbr. The sequence of reactions coupling AcAcCoA synthetase and AcAcCoA thiolase in cytoplasm may be an important pathway for generation of AcCoA from KBs for fatty acid synthesis in all regions of the developing brain. This interpretation is strengthened by evidence of concomitant increases in the activities of fatty acid synthetase and AcCoA carboxylase.