Systemic, cerebral and skeletal muscle ketone body and energy metabolism during acute hyper-D-β-hydroxybutyratemia in post-absorptive healthy males

TY - JOUR

T1 - Systemic, cerebral and skeletal muscle ketone body and energy metabolism during acute hyper-D-β-hydroxybutyratemia in post-absorptive healthy males

AU - Mikkelsen, Kristian H

AU - Seifert, Thomas

AU - Secher, Niels H

AU - Grøndal, Thomas

AU - van Hall, Gerrit

PY - 2015/2/1

Y1 - 2015/2/1

N2 - CONTEXT: 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.OBJECTIVES: The objectives of this study were to quantitate systemic, cerebral, and skeletal muscle HOB utilization and its effect on energy metabolism.DESIGN: Single trial.SETTING: Hospital.PARTICIPANT: Healthy post-absorptive males (n = 6).INTERVENTIONS: 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.MAIN OUTCOME MEASURES: 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.CONCLUSION: 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.

AB - CONTEXT: 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.OBJECTIVES: The objectives of this study were to quantitate systemic, cerebral, and skeletal muscle HOB utilization and its effect on energy metabolism.DESIGN: Single trial.SETTING: Hospital.PARTICIPANT: Healthy post-absorptive males (n = 6).INTERVENTIONS: 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.MAIN OUTCOME MEASURES: 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.CONCLUSION: 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.

U2 - 10.1210/jc.2014-2608

DO - 10.1210/jc.2014-2608

M3 - Journal article

C2 - 25415176

SN - 0021-972X

VL - 100

SP - 636

EP - 643

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 2

ER -