Inhibition of rat brain lipid synthesis in vitro by 4-hydroxybutyric acid

4-Hydroxybutyric acid (4HB) is accumulated in succinic semialdehyde dehydrogenase deficiency, an inherited metabolic disease severely affecting the CNS during postnatal development. Thus, the present study was designed to evaluate the in vitro influence of 4HB on lipid synthesis and CO2 production from [U-14C] acetate in cerebral cortex of 30-day-old Wistar rats. In the presence of 4HB, there was an inhibition of lipid synthesis in cerebral cortex prisms and homogenates. However, no inhibition of lipid synthesis occurred in the homogenates free of nuclei and mitochondria. In addition, CO2 production was inhibited by 4HB in cerebral cortex prisms, and homogenates and in the mitochondrial fraction. These results might possibly be explained by an impairment of mitochondrial metabolism by 4HB which may secondarily inhibit lipid synthesis. The results reported here may help to better understand the neuropathophysiology of 4-hydroxybutyric aciduria.