Starvation-induced changes in transport of ketone bodies across the blood-brain barrier

Abstract

The permeability of the blood brain barrier (BBB) to beta-hydroxybutyrate (beta-HB) was computed in fed and starved (five days) rats by the simultaneous measurement of cerebral blood flow (diffusible indicator method-123I-iodoantipyrine) and brain uptake of 14C-beta-HB (relative to a 3H2O reference). The results from the present study demonstrate that the movement of beta-HB across the BBB in rat is by a carrier-mediated process. During starvation, total movement (carrier-mediated and diffusionary) of this ketone body into brain was observed to be enhanced because of an increase in the diffusionary loss across the cerebral capillary. The calculated transport kinetics also suggest that the beta-HB molecule has a greater affinity for the transport (mediator) protein during starvation, although the maximal rate of uptake by brain due to a carrier processes mediated Vmax is decreased either because there is a smaller quantity of the mediating molecule or because there is trans inhibition by a high cellular concentration of beta-HB or some analog.