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The kinetics of ketone bodies was studied in normal humans by giving a combined bolus intravenous injection of labeled acetoacetate ([14C]AcAc) and D(--)-beta-hydroxybutyrate (beta-[14C]-OHB) to seven subjects after an overnight fast, on two different occasions, and by collecting frequent blood samples for 100 min. Kinetic data were analyzed with both noncompartmental and compartmental modeling techniques. A four-compartment model, representing AcAc and beta-OHB in blood and two equilibrating ketone body compartments, inside the liver and extrahepatic tissues, was chosen as the most reliable mathematical representation; it is physiologically plausible and was able to accurately fit the data. The model permitted evaluation of the in vivo rate of ketone body production in the liver, the individual plasma clearance rates of AcAc and beta-OHB, their initial volumes of distribution, and the transfer rate parameters among the four ketone body compartments. Moreover, the model provided estimates of the components of the rates of appearance of AcAc and beta-OHB in plasma due to newly synthesized ketone body from acetyl-CoA in the liver, and to interconversion and recycling in the liver and extrahepatic tissues. The model also was used to evaluate other methodologies currently employed in the analysis of ketone body turnover data: the conventional approach based on use of the combined specific activity of AcAc and beta-OHB required assumptions not satisfied in vivo, leading to substantial errors in key parameter estimates.
A simplified version courtesy of ChatGPT (hope this helps):- In this study, researchers investigated the kinetics of ketone bodies in normal human subjects. Ketone bodies, such as acetoacetate (AcAc) and D(--)-beta-hydroxybutyrate (beta-OHB), are produced in the liver during periods of fasting or low carbohydrate intake and serve as alternative energy sources for the body. The experimental setup involved giving a combined bolus intravenous injection of labeled acetoacetate ([14C]AcAc) and beta-hydroxybutyrate (beta-[14C]-OHB) to seven subjects after an overnight fast on two different occasions. Frequent blood samples were collected over a 100-minute period to track the kinetics of these labeled ketone bodies. The researchers analyzed the kinetic data using two different modeling techniques: noncompartmental and compartmental modeling. The compartmental modeling approach proved to be the most reliable mathematical representation. It involved a four-compartment model that accounted for AcAc and beta-OHB in the blood and two equilibrating ketone body compartments—one inside the liver and the other in extrahepatic tissues. The key findings and insights obtained from this modeling approach were as follows: Ketone body production in the liver: The model allowed researchers to evaluate the in vivo rate of ketone body production in the liver. Plasma clearance rates: The individual plasma clearance rates of AcAc and beta-OHB could be estimated from the model. Initial volumes of distribution: The model provided estimates of the initial volumes of distribution for AcAc and beta-OHB in the different compartments. Transfer rate parameters: The model also allowed the determination of transfer rate parameters among the four ketone body compartments, providing insights into how ketone bodies move within the body. Rates of appearance of ketone bodies in plasma: The model enabled the calculation of the rates of appearance of AcAc and beta-OHB in the plasma, considering both newly synthesized ketone body production from acetyl-CoA in the liver and interconversion and recycling processes in the liver and extrahepatic tissues. Additionally, the study compared the compartmental modeling approach with the conventional approach based on the combined specific activity of AcAc and beta-OHB. The conventional approach required certain assumptions that were not fully satisfied in vivo, leading to significant errors in key parameter estimates. The compartmental modeling, on the other hand, provided a more accurate representation of the data and a better understanding of the kinetics of ketone bodies in the body. Overall, this study sheds light on the complex metabolism of ketone bodies in humans and highlights the importance of using appropriate mathematical models to analyze kinetic data accurately. Such research has implications for understanding metabolic processes and may be relevant for conditions like fasting, diabetes, or ketogenic diets.
People follow the keto kinetics diet to promote weight loss and improve tier overall health. It involves consuming low-carb and high-fat foods to encourage the body to enter a state of ketosis, where it burns fat for energy. However, it’s always a good idea to consult with a healthcare professional before starting any new diet to ensure it’s safe and suitable for your individual needs.
