Acute high-fat high-sugar diet rapidly increases blood-brain barrier permeability in mice

Background: The blood-brain barrier (BBB) maintains brain homeostasis by protecting the brain from pathological stimuli and controlling the entry of physiological substances from the periphery. Consequently, alterations in BBB permeability may pose a threat to brain health. Long-term consumption of a high-fat high-sugar/Western diet (HFD) is known to induce BBB dysfunction. However, nothing is known about the immediate effects of acute HFD consumption on the BBB. Methods: After consumption of either HFD or standard chow, mice were injected into the tail vein with fluorescent tracers of different sizes, including the drug doxorubicin. Individual brain regions were homogenized and analyzed for tracer extravasation using spectrophotometry. Localized tracer leakage over time in the somatosensory cortex was studied using high-resolution in vivo 2-photon microscopy. Results: We demonstrate region-specific BBB leakage already after 1 hour of HFD for low- and high-molecular-weight tracers. Acute HFD also significantly increased BBB permeability to the anticancer drug doxorubicin. Conclusion: These previously unknown effects of acute HFD may have direct and drastic implications for the clinical use of drugs depending on the dietary habits of the patient.