• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.37-45
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• 2019

To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly ${\beta}$-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-ketoacid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other $K_{ATP}$ channel openers.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.3
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• pp.69-77
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• 2018

Pregnancy and delivery pose a high risk of developing metabolic decompensation in women with defects of ketone body metabolism. In this review, the available reported cases in pregnancy are summarized. It is very important to properly manage women with defects of ketone body metabolism during pregnancy, especially nausea and vomiting in the first trimester of pregnancy, and during labor and delivery. Pregnant women with deficiencies of HMG-CoA lyase or succinyl-CoA:3-ketoacid CoA transferase (SCOT) often experience metabolic decompensations with nausea and vomiting of pregnancy, often requiring hospitalization. For successful delivery and to reduce stresses, vaginal delivery with epidural anesthesia or elective cesarean delivery with epidural or spinal anesthesia are recommended for women with HMG-CoA lyase and SCOT deficiency. In beta-ketothiolase deficiency, four pregnancies in three patients had favorable outcomes without severe metabolic problems.

• Analytical Science and Technology
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• v.36 no.4
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• pp.170-179
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• 2023

Starvation, diabetes, alcoholism and hypothermia cause ketoacidosis in the human body; therefore, the cause of death can be determined by analyzing ketone bodies in the blood of the deceased. In the case of decomposition of the cadaver, however, since collecting intact blood is impossible, ketone body analysis is performed using the spleen. However, the index for diagnosing ketoacidosis is based on blood concentration, and its correlation with ketone bodies present in the spleen remains unknown. In particular, since decomposition proceeds rapidly during summer, when temperature and humidity are high, understanding the correlation between ketone bodies in the blood and spleen is important to estimate the state at the time of death from a decaying body. Therefore, in the present study, the correlation between ketone bodies in the blood and spleen of the deceased was explored. Ketone bodies (beta-hydroxybutyric acid [BHB] and acetone) in the blood and spleen were analyzed and compared from autopsies (>100 mg·L^-1 BHB, blood basis) conducted at the Daejeon Forensic Research Institute from June to December 2021. Moreover, the concentration of ketone bodies in the spleen juice and tissues was compared assuming the scenario of extreme decomposition. Ketone retention concentration in the blood and spleen was positively correlated, and the ratio of BHB concentration in the spleen to BHB concentration in the blood ranged from 0.52 to 1.08 (mean = 0.85 ± 0.12), although the ratio may vary depending on the degree of decomposition of the corpse.

• Analytical Science and Technology
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• v.29 no.1
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• pp.49-55
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• 2016

A ketone body (acetoacetic acid, β-hydroxybutyric acid, and acetone) increases from blood or urine when bio-energy dependence pays more fatty acid than glucose. However, in case oxidation of fat is greater than the capacity of the citric acid cycle the fatty acid oxidation is made from acetoacetyl CoA to acetoacetate then, again form β-hydroxyburytic acid to acetone, the diffusion take place into the blood. Enzymes that oxidize ketone body in the brain and nerve tissue blood ketone dody is increased during prolonged fasting, brain used it as energy. In this study, we developed the rapid two step derivatization method for sensitive detection of the ketone body by GC-MS/SIM. The plasma was deproteinized and then the hydroxy and carboxyl groups of ketone body are subjected to extraction and drying then, keto-group were derivatized with hydoxylamine at 60℃ for 30 min for oximation. Then it was trimetyl-silylated with BSTFA at 80℃ for 30 min and analyzed using a GC-MS. The linear ranges were in between 0.001 μg/mL and 250 μg/mL for β-hydroxy butyrate, and acetoacetate. The method detection limits were below 0.1 pg over each target compound determined. The mean recoveries (%) of target compounds were ranged from 88.2 % to 92.3 % at 1 µg/mL, from 89.5 % to 94.8 % at 10 μg/mL, with RSD of 6.3-9.4 %. This method could be applied to quantification of ketone bodies which are seen in the keto-acidosis in children and adults from a variety of diseases that cause ketones in the blood and urine.

• Korean Journal of Agricultural Science
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• v.43 no.3
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• pp.394-400
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• 2016

The objective of this study was to estimate the environmental factors affecting milk ${\beta}$-hydroxybutyric acid (BHBA) and acetone (Ac) concentrations in Holstein cattle. A total of 264,221 test-day records collected from the Korea Animal Improvement Association (KAIA) during the period of 2012 to 2014 were used in this study. Analysis of variance (ANOVA) was performed to determine the factors significantly affecting ketone body concentrations. Parameters considered in the model were season of test, season of calving, parity, lactation stage, and milk collecting time (AM and PM). According to the ANOVA, the $R^2$ for milk BHBA and Ac were 0.5226 and 0.4961, respectively. 'Season of test' showed a considerable influence on ketone body concentration. Least square (LS) means for milk BHBA concentrations was the lowest ($39.04{\mu}M$) in winter while it increased up to $62.91{\mu}M$ in summer. But Ac concentration did not significantly change along with 'season of test'. The means of milk BHBA and Ac concentrations were high at first lactation stage, low around second lactation stage, and then gradually increased. Cows milked in the morning had lower mean BHBA and Ac concentrations ($48.49{\mu}M$ and $121.69{\mu}M$, respectively) in comparison to those milked in the evening ($53.46{\mu}M$ and $130.42{\mu}M$, respectively). The LS means of BHBA and Ac slightly increased over parities. These results suggest that proper maintenance of milk collection, herd management programs, and evaluation of ketone body levels in milk should be considered for the efficient management of resistance to ketosis.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.70-70
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• 2003

In mammalians, ketone bodies (acetoacetate, D(-)-3-hydroxybutyrate and acetone) are generated mainly in the liver via the 3-hydroxy-3-methylglutaryl-CoA pathway, carried to and utilized in extrahepatic tissues as an energy source during starvation and diabetes in particular due to their overproduction as the consequence of elevated fatty acid oxidation and lowered glucose metabolism. (omitted)

• Nutritional Sciences
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• v.7 no.2
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• pp.65-69
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• 2004

A study was carried out to determine the effect of a very low-carbohydrate diet on weight gain, body composition, and serum levels of cholesterol, triacylglycerol, glucose, ketone bodies and insulin. Twenty rats (mean initial weight, 212 g) were divided into two groups and each group was assigned a conventional high-carbohydrate diet (control) or a very low-carbohydrate diet containing 59.8% ground pork rind snack and fed the diet for four weeks. Average daily body weight gain was not different between the two groups during the first two weeks, but was significantly lower in rats fed the very low-carbohydrate diet than in those in the control group during third (p<0.05) and fourth weeks (p<0.01). Feedintake as well as energy intake was lower in rats fed the very low-carbohydrate diet than in those in the control group. The very low-carbohydrate diet reduced (p<0.01) serum triacylglycerol (34$\pm$83 vs 82$\pm$8 mg/l00 mL) and insulin (3.90$\pm$0.53 vs 7.60$\pm$0.61 $\mu$IU/mL) levels, while increasing (p<0.01) ketone body level (368$\pm$25 vs 236$\pm$24 $\mu$mol/L), compared with the control. Serum glucose and total cholesterol levels were not different (p>0.05) between the two dietary treatments. Proximate analysis of carcasses showed that the very low-carbohydrate diet decreased (p<0.01) body fat (26.1$\pm$1.04 vs 30.5$\pm$0.86%), while increasing (p<0.01) body protein (63.1$\pm$0.94 vs 59.4$\pm$0.70%) contents. Results indicate that short-term feeding of a very low-carbohydrate diet is beneficial for alleviating risk factors known to involve cardiovascular diseases or artherosclerosis. However, more studies with model animals as well as humans are recommended to examine the long-term health benefits of low-carbohydrate diets.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.3
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• pp.229-229
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• 2019

• Journal of Life Science
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• v.33 no.5
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• pp.436-444
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• 2023

Scientific training, diet, and ergogenic aids are widely used to overcome the limits of humans' physical abilities and to achieve excellent sports records. The adoption of nutritional strategies is important for athletes to perform at their highest level, and one of the main factors determining endurance ability is increased fat metabolism. A ketogenic diet (high fat, low carbohydrates) has thus been proposed as an alternative strategy to maximize fatty acid oxidation during prolonged periods of exercise. However, studies have shown mixed results regarding the ergogenic value of a ketogenic diet. For this reason, exogenous ketone supplements (EKS, ingestible forms of ketone bodies, ketone esters, and/or salts) have been suggested to obtain nutritional ketosis, an acute transient increase in circulating acetoacetate (AcAc) and b-hydroxybutyrate (bHB) concentrations, without limiting carbohydrate intake. Some studies have suggested the beneficial effects of EKS on the performance of endurance exercises by providing an additional fuel substrate for peripheral tissues, such as cardiac and skeletal muscles, sparing carbohydrates/increasing fat oxidation and post-exercise recovery by increasing glycogen resynthesis in the liver/muscle, attenuating protein degradation, stimulating protein synthesis in the skeletal muscle, etc. However, many studies have failed to observe the beneficial effects of EKS as an ergogenic aid. As such, this review summarizes the theoretical basis of, as well as the proposed and proven effects of EKS on exercise performance and recovery to date.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.6
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• pp.798-803
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• 2018

Objective: The objective of this study was to estimate the genetic parameters for milk ${\beta}$-hydroxybutyrate (BHBA), acetone (Ac), fat protein ratio (FPR), and energy balance (EB) using milk test day records and investigate the effect of early lactation FPR and EB on milk ketone body concentrations. Methods: Total 262,940 test-day records collected from Korea Animal Improvement Association during the period of 2012 to 2016 were used in this study. BHBA and Ac concentrations in milk were measured by Fourier transform infrared spectroscopy (FTIR). FPR values were obtained using test day records of fat and protein percentage. EB was calculated using previously developed equation based on parity, lactation week, and milk composition data. Genetic parameters were estimated by restricted maximum likelihood procedure based on repeatability model using Wombat program. Results: Elevated milk BHBA and Ac concentrations were observed during the early lactation under the negative energy balance. Milk FPR tends to decrease with the decreasing ketone body concentrations. Heritability estimates for milk BHBA, Ac, EB, and FPR ranged from 0.09 to 0.14, 0.23 to 0.31, 0.19 to 0.52, and 0.16 to 0.42 respectively at parity 1, 2, 3, and 4. The overall heritability for BHBA, Ac, EB and FPR were 0.29, 0.32, 0.58, and 0.38 respectively. A common pattern was observed in heritability of EB and FPR along with parities. Conclusion: FPR and EB can be suggested as potential predictors for risk of hyperketonemia. The heritability estimates of milk BHBA, Ac, EB, and FPR indicate that the selective breeding may contribute to maintaining the milk ketone bodies at optimum level during early lactation.