Effect of 1,3-butanediol on cerebral energy metabolism. Comparison with β-hydroxybutyrate

Abstract

Previous studies have shown that 1,3-butanediol (BD) has beneficial effects in experimental models of hypoxia or ischemia but the mechanism by which it exerts its protective effects remains unknown. BD is converted in the body to beta-hydroxybutyrate (BHB) and it has been proposed that its effects were linked to its ketogenic effect. The effects of BD (25 and 50 mmol/kg) on cerebral energy metabolism of rats were studied by measuring the cerebral level of energy metabolites and by evaluating the cerebral metabolic rate according to the Lowry's method. BD induced an increase in [cortical glucose]/[plasma glucose] ratio which was associated with a decrease in lactate level and an increase in glucose and glycogen stores. In contrast, BHB treatment which mimicked hyperketonemia equivalent to BD did not modify cerebral glycolysis metabolites. Calculation of the energy reserve flux after decapitation showed that BD did not reduce the cerebral metabolic rate excluding a protective effect due to a depressant, barbiturate-like, action. These results suggest that BD induces a reduction of cerebral glycolytic rate. However, the effect is not linked to hyperketonemia but might be due to intracerebral conversion of BD to BHB.