title: Diet-induced ketosis increases capillary density without altered blood flow in rat brain.
abstract: It is recognized that ketone bodies, such as R-beta-hydroxybutyrate (beta-HB) and acetoacetate, are energy sources for the brain. As with glucose metabolism, monocarboxylate uptake by the brain is dependent on the function and regulation of its own transporter system. We concurrently investigated ketone body influx, blood flow, and regulation of monocarboxylate transporter (MCT-1) and glucose transporter (GLUT-1) in diet-induced ketotic (KG) rat brain. Regional blood-to-brain beta-HB influx (micromol.g(-1).min(-1)) increased 40-fold with ketosis (4.8 +/- 1.8 plasmabeta-HB; mM) in all regions compared with the nonketotic groups (standard and no-fat diets); there were no changes in regional blood flow. Immunohistochemical staining revealed that GLUT-1 density (number/mm2) in the cortex was significantly elevated (40%) in the ketotic group compared with the standard and no-fat diet groups. MCT-1 was also markedly (3-fold) upregulated in the ketotic group compared with the standard diet group. In the standard diet group, 40% of the brain capillaries stained positive for MCT-1; this amount doubled with the ketotic diet. Western blot analysis of isolated microvessels from ketotic rat brain showed an eightfold increase in GLUT-1 and a threefold increase in MCT-1 compared with the standard diet group. These data suggest that diet-induced ketosis results in increased vascular density at the blood-brain barrier without changes in blood flow. The increase in extraction fraction and capillary density with increased plasma ketone bodies indicates a significant flux of substrates available for brain energy metabolism.
authors.affiliation: Department of Anatomy, Case Western Reserve University School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106-4938, USA. map10@case.edu
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Puchowicz
authors.forename: Kui
authors.initials: K
authors.lastname: Xu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.forename: Andre
authors.initials: A
authors.lastname: Ivy
authors.forename: Doug
authors.initials: D
authors.lastname: Emancipator
authors.forename: Joseph C
authors.initials: JC
authors.lastname: LaManna
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D004032:Diet; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D007662:Ketosis / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism; D014018:Tissue Distribution; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D020155:3-Hydroxybutyric Acid; D051272:Glucose Transporter Type 1; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C495679:Slc2a1 protein, rat