Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain

Richard L. Leino, David Z. Gerhart, Roman Duelli, Bradley E. Enerson, Lester R Drewes

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

Monocarboxylate transporter (MCT1) levels in brains of adult Long-Evans rats on a high-fat (ketogenic) diet were investigated using light and electron microscopic immunocytochemical methods. Rats given the ketogenic diet (91% fat and 9% protein) for up to 6 weeks had increased levels of the monocarboxylate transporter MCT1 (and of the glucose transporter GLUT1) in brain endothelial cells and neuropil compared to rats on a standard diet. In ketonemic rats, electron microscopic immunogold methods revealed an 8-fold greater MCT1 labeling in the brain endothelial cells at 4 weeks. Abluminal endothelial membranes were twice as heavily labeled as luminal membranes. In controls, luminal and abluminal labeling was not significantly different. The endothelial cytoplasmic compartment was sparsely labeled (<8% of total endothelial labeling) in all brains. Neuropil MCT1 staining was more intense throughout the brain in ketonemic rats, especially in neuropil of the molecular layer of the cerebellum, as revealed by avidin-biotin immunocytochemistry. This study demonstrates that adult rats retain the capacity to upregulate brain MCT1 levels. Furthermore, their brains react to a diet that increases monocarboxylate levels in the blood by enhancing their capability to take up both monocarboxylates (MCT1 upregulation) and glucose (GLUT1 upregulation). This may have important implications for delivery of fuel to the brain under stressful and pathological conditions, such as epilepsy and GLUT1 deficiency syndrome.

Original languageEnglish (US)
Pages (from-to)519-527
Number of pages9
JournalNeurochemistry International
Volume38
Issue number6
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
This work was supported by the Whiteside Foundation (R.L.), the National Institute of Health, NS32754 (L.D.), and the Alexander von Humboldt Foundation (R.D.).

Keywords

  • Astrocyte
  • Brain
  • Endothelium
  • GLUT1
  • Ketogenic diet
  • MCT1
  • Monocarboxylate transporters
  • Pericyte

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