RESUMO
Glucose constitutes the main source of energy for the central nervous system (CNS), its entry occurring at the blood-brain barrier (BBB) via the presence of glucose transporter 1 (GLUT1). However, under food intake restrictions, the CNS can utilize ketone bodies (KB) as an alternative source of energy. Notably, the relationship between the BBB and KBs and its effect on their glucose metabolism remains poorly understood. In this study, we investigated the effect of glucose deprivation on the brain endothelium in vitro, and supplementation with KBs using induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cell-like cells (iBMECs). Glucose-free environment significantly decreased cell metabolic activity and negatively impacted the barrier function. In addition, glucose deprivation did not increase GLUT1 expression but also resulted in a decrease in glucose uptake and glycolysis. Supplementation of glucose-deprived iBMECs monolayers with KB showed no improvement and even worsened upon treatment with acetoacetate. However, under a hypoglycemic condition in the presence of KBs, we noted a slight improvement of the barrier function, with no changes in glucose uptake. Notably, hypoglycemia and/or KB pre-treatment elicited a saturable beta-hydroxybutyrate diffusion across iBMECs monolayers, such diffusion occurred partially via an MCT1-dependent mechanism. Taken together, our study highlights the importance of glucose metabolism and the reliance of the brain endothelium on glucose and glycolysis for its function, such dependence is unlikely to be covered by KBs supplementation. In addition, KB diffusion at the BBB appeared induced by KB pre-treatment and appears to involve an MCT1-dependent mechanism.
Assuntos
Células-Tronco Pluripotentes Induzidas , Corpos Cetônicos , Ácido 3-Hidroxibutírico/farmacologia , Ácido 3-Hidroxibutírico/metabolismo , Corpos Cetônicos/metabolismo , Corpos Cetônicos/farmacologia , Células Endoteliais/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Encéfalo/metabolismo , Barreira Hematoencefálica/metabolismo , Glucose/metabolismo , Endotélio/metabolismo , Suplementos NutricionaisRESUMO
India represents one-third of the world's fluorosis burden and is the fifth global producer of bauxite ore, which has previously been identified as a potential resource for remediating fluoride-contaminated groundwater in impoverished communities. Here, we use thermal activation and/or groundwater acidification to enhance fluoride adsorption by Indian bauxite obtained from Visakhapatnam, an area proximate to endemic fluorosis regions. We compare combinatorial water treatment and bauxite-processing scenarios through batch adsorption experiments, material characterization, and detailed cost analyses. Heating Indian bauxite above 300 °C increases available surface area by > 15× (to â¼170 m2/g) through gibbsite dehydroxylation and reduces the bauxite dose for remediating 10 ppm F- to 1.5 ppm F- by â¼93% (to 21 g/L). Additionally, lowering groundwater pH to 6.0 with HCl or CO2 further reduces the average required bauxite doses by 43-73% for ores heated at 300 °C (â¼12 g/L) and 100 °C (â¼77 g/L). Product water in most examined treatment scenarios complies with EPA standards for drinking water (e.g., As, Cd, Pb, etc.) but potential leaching of Al, Mn, and Cr is of concern in some scenarios. Among the defluoridation options explored here, bauxite heated at 300 °C in acidified groundwater has the lowest direct costs ($6.86 per person per year) and material-intensity.