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

Michelle Puchowicz, Kui Xu, Xiaoyan Sun, Andre Ivy, Doug Emancipator, Joseph C. LaManna

Research output: Contribution to journalArticle

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Abstract

It is recognized that ketone bodies, such as R-β-hydroxybutyrate (β-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 β-HB influx (μmol·g -1·min-1) increased 40-fold with ketosis (4.8 ± 1.8 plasmaβ-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/mm 2) 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume292
Issue number6
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

Fingerprint

Ketosis
Nutrition
Rats
Brain
Blood
Diet
Ketone Bodies
Fats
Hydroxybutyrates
Plasmas
Facilitative Glucose Transport Proteins
Regional Blood Flow
Microvessels
Blood-Brain Barrier
Metabolism
Energy Metabolism
Blood Vessels
Western Blotting
Staining and Labeling
Fluxes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Diet-induced ketosis increases capillary density without altered blood flow in rat brain. / Puchowicz, Michelle; Xu, Kui; Sun, Xiaoyan; Ivy, Andre; Emancipator, Doug; LaManna, Joseph C.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 292, No. 6, 01.06.2007.

Research output: Contribution to journalArticle

Puchowicz, Michelle ; Xu, Kui ; Sun, Xiaoyan ; Ivy, Andre ; Emancipator, Doug ; LaManna, Joseph C. / Diet-induced ketosis increases capillary density without altered blood flow in rat brain. In: American Journal of Physiology - Endocrinology and Metabolism. 2007 ; Vol. 292, No. 6.
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