title: Specific regions of the brain are capable of fructose metabolism.
abstract: High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and non-alcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40-60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5-10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15-150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production.
authors.affiliation: Program in Molecular Biology, Cell Biology, and Biochemistry, Boston University, 5 Cummington Mall, Boston, MA, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Oppelt
authors.affiliation: Department of Biology, Boston University, 5 Cummington Mall, Boston, MA, USA. Electronic address: wanming.zhang1@gmail.com.
authors.forename: Wanming
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Program in Molecular Biology, Cell Biology, and Biochemistry, Boston University, 5 Cummington Mall, Boston, MA, USA; Department of Biology, Boston University, 5 Cummington Mall, Boston, MA, USA. Electronic address: tolan@bu.edu.
authors.forename: Dean R
authors.initials: DR
authors.lastname: Tolan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D019295:Computational Biology; D005631:Fructokinases / Q000378:metabolism; D005632:Fructose / Q000378:metabolism*; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D015870:Gene Expression; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D051296:Glucose Transporter Type 5; D006593:Hexokinase / Q000378:metabolism; D017403:In Situ Hybridization; D008099:Liver / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D051296:Glucose Transporter Type 5; C465351:Slc2a5 protein, mouse; C498775:Slc2a9 protein, mouse; D005632:Fructose; D005631:Fructokinases; D006593:Hexokinase; C021475:ketohexokinase; D005634:Fructose-Bisphosphate Aldolase
keywords: Brain energy metabolism; Fructose toxicity; Fructose transporters