Dual-isotope technique for determination of in vivo ketone body kinetics
Total ketone body specific activity has been widely used in studies of ketone body metabolism to circumvent so-called isotope disequilibrium between the two major ketone body pools, acetoacetate and beta-hydroxybutyrate. Recently, this approach has been criticized on theoretical grounds. In the present studies, (13C)acetoacetate and beta-(14C)hydroxybutyrate were simultaneously infused in nine mongrel dogs before and during an infusion of either unlabeled sodium acetoacetate or unlabeled sodium beta-hydroxybutyrate. Ketone body turnover was determined using total ketone body specific activity, total ketone body moles % enrichment, and an open two-pool model, both before and during the exogenous infusion of unlabeled ketone bodies. Basal ketone body turnover rates were significantly higher using (13C)acetoacetate than with either beta-(14C)hydroxybutyrate alone or the dual-isotope model (3.6 +/- 0.5 vs. 2.2 +/- 0.2 and 2.7 +/- 0.2 mumol X kg-1 X min-1, respectively, P less than 0.05). During exogenous infusion of unlabeled sodium acetoacetate, the dual-isotope model provided the best estimate of ketone body inflow, whereas 14C specific activity underestimated the known rate of acetoacetate infusion by 55% (P less than 0.02). During sodium beta-hydroxybutyrate infusion, (13C)-acetoacetate overestimated ketone body inflow by 55% (P = NS), while better results were obtained with 14C beta-hydroxybutyrate alone and the two-pool model. Ketone body interconversion as estimated by the dual-isotope technique increased markedly during exogenous ketone body infusion. In conclusion, significant errors in estimation of ketone body inflow were made using single-isotope techniques, whereas a dual-isotope model provided reasonably accurate estimates of ketone body inflow during infusion of exogenous acetoacetate and beta-hydroxybutyrate.
- Research Organization:
- Mayo Foundation, Rochester, MN
- OSTI ID:
- 5018932
- Journal Information:
- Am. J. Physiol.; (United States), Journal Name: Am. J. Physiol.; (United States)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
KETONES
DUAL-ISOTOPE SUBTRACTION TECHNIQUE
METABOLISM
ACCURACY
ACETOACETATES
BODY COMPOSITION
BUTYRIC ACID
CARBON 13
CARBON 14 COMPOUNDS
DOGS
ESTERS
MEASURING METHODS
ANIMALS
CARBON ISOTOPES
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
EVEN-ODD NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
MAMMALS
MONOCARBOXYLIC ACIDS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
STABLE ISOTOPES
TRACER TECHNIQUES
VERTEBRATES
550501* - Metabolism- Tracer Techniques