title: Systemic, cerebral and skeletal muscle ketone body and energy metabolism during acute hyper-D-β-hydroxybutyratemia in post-absorptive healthy males.
abstract: BACKGROUND
  Ketone bodies are substrates during fasting and when on a ketogenic diet not the least for the brain and implicated in the management of epileptic seizures and dementia. Moreover, D-β-hydroxybutyrate (HOB) is suggested to reduce blood glucose and fatty acid levels.
  
  
  OBJECTIVE
  The objectives of this study were to quantitate systemic, cerebral, and skeletal muscle HOB utilization and its effect on energy metabolism.
  
  
  METHODS
  Single trial.
  
  
  METHODS
  Hospital.
  
  
  METHODS
  Healthy post-absorptive males (n = 6).
  
  
  METHODS
  Subjects were studied under basal condition and three consecutive 1-hour periods with a 3-, 6-, and 12-fold increased HOB concentration via HOB infusion.
  
  
  METHODS
  Systemic, cerebral, and skeletal muscle HOB kinetics, oxidation, glucose turnover, and lipolysis via arterial, jugular, and femoral venous differences in combination with stable isotopically labeled HOB, glucose, and glycerol, infusion.
  
  
  RESULTS
  An increase in HOB from the basal 160-450 μmol/L elicited 14 ± 2% reduction (P = .03) in glucose appearance and 37 ± 4% decrease (P = .03) in lipolytic rate while insulin and glucagon were unchanged. Endogenous HOB appearance was reduced in a dose-dependent manner with complete inhibition at the highest HOB concentration (1.7 mmol/L). Cerebral HOB uptake and subsequent oxidation was linearly related to the arterial HOB concentration. Resting skeletal muscle HOB uptake showed saturation kinetics.
  
  
  CONCLUSIONS
  A small increase in the HOB concentration decreases glucose production and lipolysis in post-absorptive healthy males. Moreover, cerebral HOB uptake and oxidation rates are linearly related to the arterial HOB concentration of importance for modifying brain energy utilization, potentially of relevance for patients with epileptic seizures and dementia.
authors.affiliation: Clinical Metabolomics Core Facility (K.H.M., T.G., G.v.H.), Department of Anaesthesiology (T.S., N.H.S.), Rigshospitalet, and Department of Biomedical Sciences (G.v.H.), Faculty of Health and Medical Sciences, University of DK-2100 Copenhagen, Denmark.
authors.forename: Kristian H
authors.initials: KH
authors.lastname: Mikkelsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Seifert
authors.forename: Niels H
authors.initials: NH
authors.lastname: Secher
authors.forename: Thomas
authors.initials: T
authors.lastname: Grøndal
authors.forename: Gerrit
authors.initials: G
authors.lastname: van Hall
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007657:Ketone Bodies; D020155:3-Hydroxybutyric Acid