• Title/Summary/Keyword: Ketone body metabolism

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Defects in Ketone Body Metabolism and Pregnancy

  • Fukao, Toshiyuki
    • 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.

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Nicorandil alleviated cardiac hypoxia/reoxygenation-induced cytotoxicity via upregulating ketone body metabolism and ACAT1 activity

  • Bai, Yan Ping;Han, Lei Sen
    • 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.

Acetoacetyl-CoA Synthetase, a Novel Cytosolic Ketone Body-Utilizing Enzyme that Specifically Activates Acetoacetate to its Coenzyme A Ester

  • Fukui, Tetsuya
    • 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)

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Effects of Ketone Body Supplementation on Exercise Performance, Post-exercise Recovery, and Muscle Protein Metabolism (케톤 보충제가 운동수행능력, 운동 후 회복, 및 근육 단백질 대사에 미치는 영향)

  • Jeong-sun Ju;Yi Sub Kwak
    • 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.

Ketone ester supplementation of Atkins-type diet prolongs survival in an orthotopic xenograft model of glioblastoma

  • Hassan Azari;Angela Poff;Dominic D'Agostino;Brent Reynolds
    • Anatomy and Cell Biology
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    • v.57 no.1
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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.

Gene Expression Profiling of Liver and Mammary Tissues of Lactating Dairy Cows

  • Baik, M.;Etchebarne, B.E.;Bong, J.;VandeHaar, M.J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.6
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    • pp.871-884
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    • 2009
  • Gene expression profiling is a useful tool for identifying critical genes and pathways in metabolism. The objective of this study was to determine the major differences in the expression of genes associated with metabolism and metabolic regulation in liver and mammary tissues of lactating cows. We used the Michigan State University bovine metabolism (BMET) microarray; previously, we have designed a bovine metabolism-focused microarray containing known genes of metabolic interest using publicly available genomic internet database resources. This is a high-density array of 70mer oligonucleotides representing 2,349 bovine genes. The expression of 922 genes was different at p<0.05, and 398 genes (17%) were differentially expressed by two-fold or more with 222 higher in liver and 176 higher in mammary tissue. Gene ontology categories with a high percentage of genes more highly expressed in liver than mammary tissues included carbohydrate metabolism (glycolysis, glucoenogenesis, propanoate metabolism, butanoate metabolism, electron carrier and donor activity), lipid metabolism (fatty acid oxidation, chylomicron/lipid transport, bile acid metabolism, cholesterol metabolism, steroid metabolism, ketone body formation), and amino acid/nitrogen metabolism (amino acid biosynthetic process, amino acid catabolic process, urea cycle, and glutathione metabolic process). Categories with more genes highly expressed in mammary than liver tissue included amino acid and sugar transporters and MAPK, Wnt, and JAK-STAT signaling pathways. Real-time PCR analysis showed consistent results with those of microarray analysis for all 12 genes tested. In conclusion, microarray analyses clearly identified differential gene expression profiles between hepatic and mammary tissues that are consistent with the differences in metabolism of these two tissues. This study enables understanding of the molecular basis of metabolic adaptation of the liver and mammary gland during lactation in bovine species.

Clinical Significance of Urinalysis with Test Strips (복합시험지법(複合試驗紙法)에 의한 이상뇨(異常尿) 검사(檢査)의 임상적(臨床的) 의의(意義))

  • Sohn, Tai-Hyu
    • The Journal of the Korean life insurance medical association
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    • v.2 no.1
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    • pp.75-81
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    • 1985
  • Urine contains protein and nucleic acid(urea, uric acid, creatinine, ammonia, amino acids), various organic and inorganic materials, vitamin, hormone, enzyme etc. The examination of gualitative or quantitative change of the above mentioned materials and picking up the abnormal materials are useful to diagnose diseases. The test strip for examination of urine is applied to the routine test, monitoring of medical therapy and recurrence, self monitoring, and screeing in preventive medicine. We have been using multitest strip for checking the bacterial infection(nitrite), PH, protein, glucose, ketone body, urobilinogen, bilirubin and occult blood. So it is possible to diagnose three groups of diseases as follows, abnormal metabolism of the carbohydrate, diseases of kidney and other urogenital system, diseases of hepatobiliary system and hemolytic disease causing abnormal metabolism of bile juice.

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Effects of Starvation on Lipid Metabolism and Gluconeogenesis in Yak

  • Yu, Xiaoqiang;Peng, Quanhui;Luo, Xiaolin;An, Tianwu;Guan, Jiuqiang;Wang, Zhisheng
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.11
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    • pp.1593-1600
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    • 2016
  • This research was conducted to investigate the physiological consequences of undernourished yak. Twelve Maiwa yak ($110.3{\pm}5.85kg$) were randomly divided into two groups (baseline and starvation group). The yak of baseline group were slaughtered at day 0, while the other group of yak were kept in shed without feed but allowed free access to water, salt and free movement for 9 days. Blood samples of the starvation group were collected on day 0, 1, 2, 3, 5, 7, 9 and the starved yak were slaughtered after the final blood sample collection. The liver and muscle glycogen of the starvation group decreased (p<0.01), and the lipid content also decreased while the content of moisture and ash increased (p<0.05) both in Longissimus dorsi and liver compared with the baseline group. The plasma insulin and glucose of the starved yak decreased at first and then kept stable but at a relatively lower level during the following days (p<0.01). On the contrary, the non-esterified fatty acids was increased (p<0.01). Beyond our expectation, the ketone bodies of ${\beta}$-hydroxybutyric acid and acetoacetic acid decreased with prolonged starvation (p<0.01). Furthermore, the mRNA expression of lipogenetic enzyme fatty acid synthase and lipoprotein lipase in subcutaneous adipose tissue of starved yak were down-regulated (p<0.01), whereas the mRNA expression of lipolytic enzyme carnitine palmitoyltransferase-1 and hormone sensitive lipase were up-regulated (p<0.01) after 9 days of starvation. The phosphoenolpyruvate carboxykinase and pyruvate carboxylase, responsible for hepatic gluconeogenesis were up-regulated (p<0.01). It was concluded that yak derive energy by gluconeogenesis promotion and fat storage mobilization during starvation but without ketone body accumulation in the plasma.

Dietary supplementation of Eucommia leaf extract to growing-finishing pigs alters muscle metabolism and improves meat quality

  • Zhenglei Shen;Chuxin Liu;Chuangye Deng;Qiuping Guo;Fengna Li;Qingwu W. Shen
    • Animal Bioscience
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    • v.37 no.4
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    • pp.697-708
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    • 2024
  • Objective: The objective of this study was to investigate the influence of dietary supplementation of Eucommia ulmoides leaf extract (ELE) on muscle metabolism and meat quality of pigs with and without pre-slaughter transportation. Methods: In a 43-day feeding experiment, a total of 160 pigs with an initial body weight 60.00±2.00 kg were randomly assigned into four groups in a completely randomized design with 10 replicates. Pigs in groups A and C were fed a basal diet and pigs in groups B and D were fed a basal diet supplemented with 0.5% ELE. Pigs were slaughtered with (group B and D) or without (group A and C) pre-slaughter transport. Muscle chemical composition, postmortem glycolysis, meat quality and muscle metabolome were analyzed. Results: Dietary ELE supplementation had no effect on the proximate composition of porcine muscle, but increased free phenylalanine, proline, citruline, norvaline, and the total free amino acids in muscle. In addition, dietary ELE increased decanoic acid and eicosapentaenoic acid, but decreased heptadecanoic acid, oleic acid, trans-oleic acid, and monounsaturated fatty acids in muscle. Meat quality measurement demonstrated that ELE improved meat water holding capacity and eliminated the negative effects of pre-slaughter transport on meat cooking yield and tenderness. Dietary ELE reduced muscle glycolytic potential, inhibited glycolysis and muscle pH decline in the postmortem conversion of muscle to meat and increased the activity of citrate synthase in muscle. Metabolomics analysis by liquid chromatographic tandem mass spectrometric showed that ELE enhanced muscle energy level, regulated AMP-activated protein kinase (AMPK) signaling, modulated glycogenolysis/glycolysis, and altered the metabolism of carbohydrate, fatty acids, ketone bodies, amino acids, purine, and pyrimidine. Conclusion: Dietary ELE improved meat quality and alleviated the negative effect of pre-slaughter transport on meat quality by enhancing muscle oxidative metabolism capacity and inhibiting glycolysis in postmortem muscle, which is probably involved its regulation of AMPK.