• The Korean Journal of Physiology and Pharmacology
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• 제23권1호
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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.

• 대한유전성대사질환학회지
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• 제18권3호
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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.

• 분석과학
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• 제36권4호
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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.

• 분석과학
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• 제29권1호
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• pp.49-55
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• 2016

케톤체는 생체 에너지 생산과정이 탄수화물보다는 지방산의 의존도가 높을 때 생성되며, 과도한 분비는 당뇨병성 케토시스나 선천성 유전성 대사이상질환을 의심할 수 있는 근거가 된다. 따라서 이의 신속 정확한 분석법의 개발이 필요하다. 본 연구에서는 혈장을 제단백한 후 hydroxylamine을 가하여 60 ℃에서 30 분간 반응시켜 oximation 후 BSTFA를 가한 후 trimethylsilylation 유도체화하여 혈장 중에서 케톤체를 신속하게 정량할 수 있는 GC-MS/SIM 분석법을 개발하였다. 케톤체의 직선성의 범위는 0.001-250 μg/mL 이었고, 혈장에서의 검출한계는 0.1 pg 이었다. 직선성을 가지는 범위에서의 상관계수(R2)는 0.998-0.999이었고, 회수율은 1 μg/mL의 표준품을 첨가하였을 때 88.2-92.3 %, 10 μg/mL의 농도를 첨가하였을 때 89.5-94.8 % 였으며 RSD는 6.3-9.4 %였다. 이 분석법을 정상인과 케토시스 환자의 검체에 적용하여 벨리데이션 하였으며, 본 분석방법은 어린이나 성인의 당뇨성 케토시스나 여러 유전성대사질환 환자 중 케토시스를 보이는 환자의 혈장 중 β-hydroxybutyric acid/acetoacetic acid의 비를 계산하여 케톤체를 신속하고 효율적으로 임상검체 분석에 응용할 수 있음을 보여주었다.

• 농업과학연구
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• 제43권3호
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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.

• Anatomy and Cell Biology
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• 제57권1호
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• pp.97-104
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• 2024

Heavy reliance on glucose metabolism and a reduced capacity to use ketone bodies makes glioblastoma (GBM) a promising candidate for ketone-based therapies. Ketogenic diet (KD) is well-known for its promising effects in controlling tumor growth in GBM. Moreover, synthetic ketone ester (KE) has demonstrated to increase blood ketone levels and enhance animal survival in a metastatic VM-M3 murine tumor model. Here, we compared the efficacy of a KE-supplemented Atkins-type diet (ATD-KE) to a classic KD in controlling tumor progression and enhancing survival in a clinically relevant orthotopic patient-derived xenograft GBM model. Our findings demonstrate that ATD-KE preserves body weight (percent change from the baseline; 112±2.99 vs. 116.9±2.52 and 104.8±3.67), decreases blood glucose (80.55±0.86 vs. 118.6±9.51 and 52.35±3.89 mg/dl), and increases ketone bodies in blood (1.15±0.03 mM vs. 0.55±0.04 and 2.66±0.21 mM) and brain tumor tissue (3.35±0.30 mM vs. 2.04±0.3 and 4.25±0.25 mM) comparable to the KD (results presented for ATD-KE vs. standard diet [STD] and KD, respectively). Importantly, the ATD-KE treatment significantly enhanced survival compared to the STD and was indistinguishable from the KD (47 days in STD vs. 56 days in KD and ATD-KE), suggesting that a nutritionally balanced low carbohydrate ATD combined with KE may be as effective as the KD alone in reducing brain tumor progression. Overall, these data support the rationale for clinical testing of KE-supplemented low-carb diet as an adjunct treatment for brain tumor patients.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-1
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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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• 제7권2호
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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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• 제23권3호
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• pp.229-229
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• 2019

• 생명과학회지
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• 제33권5호
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• pp.436-444
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• 2023

스포츠과학에서 좋은 기록을 달성하기 위해 과학적 훈련, 식단 및 운동수행증진 보조제가 널리 사용되어 왔다. 운동선수가 최고 수준의 경기력을 발휘하기 위해서는 영양학적 전략이 중요하며, 그 중 지구력 운동 수행력을 결정하는 주요 요인 중 하나는 지방대사의 증가라고 할 수 있다. 장기간 운동하는 동안 지방산 대사를 최대화하기 위한 방법으로 케톤 생성 식단(고지방, 저탄수화물)이 제안되었다. 현재까지의 연구들은 케톤 생성 식단의 에너지 생성 가치에 대해 상반된 결과를 보여주었다. 이러한 이유로 탄수화물 섭취를 제한하지 않고 영양적 케톤증(아세토아세테이트와 베타-하이드록시뷰티레이트의 급성/일시적 혈중 농도증가)을 얻기 위해 케톤 보충제(케톤 에스테르 및 케톤염)를 사용하는 것이 제안되었다. 일부 연구에서는 심장 및 골격근과 같은 말초 조직에 추가적인 연료 기질 제공, 탄수화물 절약/지방 산화 증가, 간/근육에서 글리코겐 재합성을 증가시켜 운동 후 회복에 케톤 보충제가 지구력 운동 수행에 유익한 효과를 보여주었다. 그러나 많은 연구에서 케톤 보충제가 운동수행능력 보조제로서의 유익한 효과가 나타나지 않았다. 따라서 본 연구는 현재까지의 운동 수행 및 회복 그리고 골격근 단백질 대사와 관련된 선행연구들의 케톤 보충제의 증명된 효과와 운동수행능력 증진 보조제로서의 가능성을 분석하고자 하였다.