title: A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth.
abstract: The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis. Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models.
  
  
  
  Ketone body oxidation was studied using (13)C MR spectroscopy in combination with infusion of a (13)C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models. The level of ketone body oxidation was compared with nontumorous cortical brain tissue.
  
  
  
  The level of (13)C-beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas.
  
  
  
  These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet. Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism.
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Henk M
authors.initials: HM
authors.lastname: De Feyter
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Behar
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Jyotsna U
authors.initials: JU
authors.lastname: Rao
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Kirby
authors.initials: K
authors.lastname: Madden-Hennessey
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Ip
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Fahmeed
authors.initials: F
authors.lastname: Hyder
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Lester R
authors.initials: LR
authors.lastname: Drewes
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Geschwind
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Robin A
authors.initials: RA
authors.lastname: de Graaf
authors.affiliation: Department of Radiology and Biomedical Imaging, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (H.M.D.F., J.U.R., K.M.-H., K.L.I., J.-F.G., R.A.D., D.L.R.); Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut (K.L.B.); Department of Biomedical Sciences, University of Minnesota, Duluth, Minnesota (L.R.D.); Department of Biomedical Engineering, Yale University, New Haven, Connecticut (F.H., R.A.D., D.L.R.).
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rothman
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D055423:Diet, Ketogenic; D004195:Disease Models, Animal; D005910:Glioma / Q000178:diet therapy* / Q000378:metabolism*; D007657:Ketone Bodies / Q000378:metabolism; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D011916:Rats, Inbred F344; D016019:Survival Analysis; D027981:Symporters / Q000378:metabolism; D047368:Tumor Burden; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D020155:3-Hydroxybutyric Acid; D007657:Ketone Bodies; D027501:Monocarboxylic Acid Transporters; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1
keywords: 13C MRS; MCT1; glioma; ketogenic diet; metabolism