Fasting upregulates the monocarboxylate transporter MCT1 at the rat blood-brain barrier through PPAR δ activation.
Level 5 - mechanism / opinion, no new human data
Preclinical in vivo animal and in vitro cell culture study
PubMed 38589879 · doi:10.1186/s12987-024-00526-8
What was done
Male rats were fed ad libitum or fasted for one to three days. Brain endothelial cells were acutely purified and analyzed by RNA-Seq, while isolated brain microvessels were evaluated for transporter protein expression via Western blot. Monocarboxylate transporter 1 (MCT1) activity was assessed using in situ brain perfusion. Molecular mechanisms were investigated in primary cultured rat brain endothelial cells treated with PPAR-delta agonists and free fatty acids, and rats were treated with a PPAR-delta antagonist in vivo.
What was found
No numerical values or effect sizes were reported in the abstract. Fasting did not alter the expression of major ATP-binding cassette drug efflux transporters or P-glycoprotein activity at the blood-brain barrier, but selectively modulated solute carrier transporters, including upregulating MCT1 expression and transport activity. In vivo and in vitro experiments showed that fasting activated PPAR-delta, and pharmacological antagonism of PPAR-delta prevented the fasting-induced upregulation of MCT1.
Why it matters
This study defines a mechanism by which fasting enhances ketone body transport capacity across the blood-brain barrier through PPAR-delta signaling without perturbing major drug efflux pathways.
Limits
All findings are derived from male rodents and in vitro rat endothelial cultures, limiting direct translation to human physiology. The abstract reports no sample sizes (n is unstated), confidence intervals, or numerical measurements. Female animals were not evaluated, and functional outcomes beyond transport kinetics were not assessed.
Cited by
- contradicts Fasting and ketogenic diets increase the permeability of the blood-brain barrier to various compounds and drugs.