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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/E1607    most recent 00512.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Puchowicz, M. A. Articles by LaManna, J. C. Search for Related Content PubMed PubMed Citation Articles by Puchowicz, M. A. Articles by LaManna, J. C.

Diet-induced ketosis increases capillary density without altered blood flow in rat brain

Department of Anatomy, School of Medicine, Case Western Reserve University, Cleveland, Ohio

Submitted 21 September 2006 ; accepted in final form 31 January 2007

It is recognized that ketone bodies, such as R--hydroxybutyrate (-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 -HB influx (µmol·g^–1·min^–1) increased 40-fold with ketosis (4.8 ± 1.8 plasma-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.

ketone bodies; monocarboxylate transporter-1; GLUT-1; -hydroxybutyrate; brain metabolism; blood-brain barrier