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 capi…
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Lactate and ketone bodies transported into the brain are utilized as alternative energy metabolites by the brain.
“and then utilized as alternative energy metabolites by the brain (487).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [487]
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Common Pathways in Depression and Obesity: The Role of Gut Microbiome and Diets
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- Authors
- Puchowicz, M. A., Xu, K., Sun, X., Ivy, A., Emancipator, D., & LaManna, J. C.
- Affiliations
- Case Western Reserve University (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2007-06
- Volume
- 292
- Issue
- 6
- Pages
- E1607-E1615
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2163720659
- Cited by
- 69
- References
- 45
- Citations by year
- 2026: 2 · 2024: 3 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 5 · 2015: 3 · 2014: 6 · 2013: 4 · 2012: 3
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM 066309, P50GM066309)
- National Institute of Neurological Disorders and Stroke (NS46074, R01NS046074)
- Topics
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- ketone bodies, beta-hydroxybutyrate, acetoacetate, blood flow, GLUT1, MCT1, monocarboxylate transport, glucose transport, blood-brain barrier, brain energy metabolism, high-fat diet, rat brain
- MeSH terms
- Monocarboxylate Transport Protein 1, Animals, Blood Vessels, Blood-Brain Barrier, Brain, Capillaries, Cerebrovascular Circulation, Diet, Ketosis, Male, Microcirculation, Osmolar Concentration, Tissue Distribution, Rats, Wistar, 3-Hydroxybutyric Acid, Monocarboxylic Acid Transporters, Symporters, Glucose Transporter Type 1, Rats
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