• Asian-Australasian Journal of Animal Sciences
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• v.23 no.1
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• pp.47-51
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• 2010

The objective of this study was to understand changes of plasma metabolites, hormones, and mRNA level of cytoplasmic phosphoenolpyruvate carboxykinase (PEPCK-C) in liver in spontaneous clinical ketosis; 10 clinically ketotic cows and 10 healthy cows were chosen from the same dairy farm. Eleven blood parameters and liver fat content were measured in all cows, and mRNA levels of PEPCK-C in liver were measured by semi-quantitative reverse transcription (RT) polymerase chain reaction (PCR). In ketotic cows, concentration of plasma glucose decreased (p<0.01), concentration of plasma nonesterified fatty acids (NEFA) and $\beta$-hydroxybutyric acid (BHBA) increased (p<0.01), liver fat content (18.8% wet weight) and activity of plasma aspartate aminotransferase (AST) increased (p<0.01), but concentration of plasma total bilirubin (TBIL), $\gamma$-glutamyl transpeptidase ($\gamma$-GT), and cholinesterase (CHE) increased (p>0.05). In addition, concentration of plasma insulin decreased (p<0.05), concentration of plasma glucagons decreased (p>0.05), and mRNA level of PEPCK-C in liver increased (p<0.05). It is concluded that the adaptative changes of metabolites, hormones, and mRNA level of PEPCK-C in ketotic cows were in favor of the enhancement of gluconeogenesis, the decrease of fat mobilization and the relief of ketosis, but these were still inadequate to relieve ketosis.

• Journal of Environmental Health Sciences
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• v.19 no.3
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• pp.58-63
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• 1993

In order to elucidate the alteration of drug-metabolizing enzymes and mechanism in the animal with hepatic injury and ketosis, the regulation of P450IIE was studied in the rats with heaptic injury caused by CCl$_4$ and with ketosis caused by streptozotocin and high-fat diet. P450IIE expression in liver was examined by the combination of enzyme activities, Western immunoblot, and mRNA Northern blot analyses using specific polyclonal antibody and cDNA probe for P450IIE. Enzyme activity and amounts of immunoreactive P450IIE were rapidly decreased in a time-dependent manner after a single dose of CCl$_4$ . However, the decreases in P450IIE enzyme activity and immunoreactive protein by CCl$_4$ were not accompanied by a decline in its mRNA level. The data thus suggested a post-translational reduction of P450IIE by CCl$_4$. The enzyme activities (aniline hydroxylase) in hepatic microsomes were elevated about 2-3-fold by streptozotocin and feeding with a high fat diet. This increases in enzyme activities were also accompanied by 3-fold increases in immunoreactive P450IIE protein and its mRNA. Our data thus indicated that P450IIE induction during the ketosis appears to be due to pretranslational activation.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.7
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• pp.1003-1010
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• 2008

The objective of the present study was to identify differences in the expression levels of liver proteins between healthy and ketotic cows, establish a liver metabolic interrelationship of ketosis and elucidate the metabolic characteristics of the liver during ketosis. Liver samples from 8 healthy multiparous Hostein cows and 8 ketotic cows were pooled by health status and the proteins were separated by two-dimensional-electrophoresis (2D-E). Statistical analysis of gels was performed using PDQuest software 8.0. The differences in the expression levels of liver proteins (p<0.05) between ketotic and healthy cows were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF-TOF) tandem mass spectrometry. Five enzymes/proteins were identified as being differentially expressed in the livers of ketotic cows: expression of 3-hydroxyacyl-CoA dehydrogenase type-2 (HCDH), acetyl-coenzyme A acetyltransferase 2 (ACAT) and elongation factor Tu (EF-Tu) were down-regulated, whereas that of alpha-enolase and creatine kinase were up-regulated. On the basis of this evidence, it could be presumed that the decreased expression of HCDH, which is caused by high concentrations of acetyl-CoA in hepatic cells, in the livers of ketotic cows, implies reduced fatty acid ??oxidation. The resultant high concentrations of acetyl-CoA and acetoacetyl CoA would depress the level of ACAT and generate more ??hydroxybutyric acid; high concentrations of acetyl-CoA would also accelerate the Krebs Cycle and produce more ATP, which is stored as phosphocreatine, as a consequence of increased expression of creatine kinase. The low expression level of elongation factor Tu in the livers of ketotic cows indicates decreased levels of protein synthesis due to the limited availability of amino acids, because the most glucogenic amino acids sustain the glyconeogenesis pathway; thus increasing the level of alpha-enolase. Decreased protein synthesis also promotes the conversion of amino acids to oxaloacetate, which drives the Krebs Cycle under conditions of high levels of acetyl-CoA. It is concluded that the livers of ketotic cows possess high concentrations of acetyl-CoA, which through negative feedback inhibited fatty acid oxidation; show decreased fatty acid oxidation, ketogenesis and protein synthesis; and increased gluconeogenesis and energy production.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.12
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• pp.1930-1939
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• 2020

Objective: This study was conducted to investigate the differences in several serum adipokines in perinatal dairy cows with type I and II ketosis, and the correlations between these adipokines and the two types of ketosis. Methods: Serum adiponectin (ADP), leptin (LEP), resistin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels, and energy balance indicators related to ketosis were measured. Type I and II ketosis were distinguished by serum glucose (Glu) and Y values and the correlations between adipokines in the two types of ketosis were analyzed. Results: β-Hydroxybutyric acid of type I ketosis cows was significantly negatively correlated with insulin (INS) and LEP and had a significant positive correlation with serum ADP. In type II ketosis cows, ADP and LEP were significantly negatively correlated, and INS and resistin were significantly positively correlated. Revised quantitative INS sensitivity check index (RQUICKI) values had a significantly positive correlation with ADP and had a very significant and significant negative correlation with resistin, TNF-α, and IL-6. ADP was significantly negatively correlated with resistin and TNF-α, LEP had a significantly positive correlation with TNF-α, and a significantly positive correlation was shown among resistin, IL-6, and TNF-α. There was also a significant positive correlation between IL-6 and TNF-α. Conclusion: INS, ADP, and LEP might exert biological influences to help the body recover from negative energy balance, whereas resistin, TNF-α, and IL-6 in type II ketosis cows exacerbated INS resistance and inhibited the production and secretion of ADP, weakened INS sensitivity, and liver protection function, and aggravated ketosis.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.3
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• pp.312-317
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• 2010

Complete oxidation of fatty acid in the liver of ketotic cows was investigated. Serum non-esterified fatty acid (NEFA), beta-hydroxybutyric acid (BHBA) and glucose concentrations were measured using biochemical techniques. Carnitine palmitoyl transferase II (CPT II), 3-hydroxy acyl-CoA dehydrogenase (HAD) and oxaloacetic acid (OAA) concentrations in the liver were detected by ELISA. Serum glucose was lower in ketotic cows than controls (p<0.05). Serum BHBA and NEFA concentrations were higher in ketotic cows than controls (p<0.05). OAA, CPT II, and HAD contents in the liver of ketotic cows were lower than in controls (p<0.05). There were negative correlations between serum NEFA concentration and OAA, CPT II and HAD, but no correlation between serum BHBA concentration and capacity for complete oxidation of fatty acid. Overall, the capacity for complete fatty acid oxidation in the liver of ketotic cows might have been decreased. High serum NEFA concentrations may be unfavorable factors for the pathway of complete oxidation of fatty acid in the liver.

• Journal of Veterinary Clinics
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• v.36 no.1
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• pp.68-73
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• 2019

We determined the risk factors for displacement of the abomasum (DA), and the relationships between DA and postpartum disorders, milk yield, and reproductive performance in dairy cows. Initially, we identified the risk factors for DA using data regarding cow health and calving season from 2,208 lactations. Then, we compared the incidence of postpartum disorders, culling, death, and reproductive performance between cows with DA and their control herdmates (each n = 57). In addition, serum metabolites concentrations and milk yield were compared between cows with DA and controls (each n = 33). Ketosis (odds ratio [OR] = 9.27, p < 0.0001) and twin calves (p = 0.06) increased the risk of DA. Cows with a parity of three had a higher risk (OR = 5.23, p < 0.01) of DA than primiparous cows. Serum total cholesterol concentration was lower but non-esterified fatty acid, ${\beta}-hydroxybutyrate$, and alanine aminotransferase concentrations were higher after calving in cows with DA than in controls (p < 0.05). The removal rate from the herd by 2 months after calving was higher (p < 0.05) but milk yield 1 and 2 months after calving (p < 0.01) and the rate of first insemination by 150 days postpartum were lower (hazard ratio = 0.49, p < 0.05) in cows with DA than controls. In conclusion, higher parity, twin calves, and ketosis are risk factors for DA in dairy cows, which is associated with a higher removal rate from the herd, lower milk yield, a longer calving to first insemination interval, and unfavorable levels of metabolites related to energy and liver function.

• Journal of Veterinary Clinics
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• v.10 no.2
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• pp.147-155
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• 1993

This study was carried out to investigate the Preventive and treatment effects of mixed compound of vitamin E and selenium, and ursodeoxycholic acid on the pre-parturient and post-parturient fatty liver of high. yielding dairy cows. Thirty pregnant dairy cows(2 weeks preparturition) were divided into clinical(13cows) and subclinical(17 cows) groups based upon blood chemical values, blood serum protein levels and clinical symptoms. The clinical group was subdivided into treated clinical group(6 cows) and non-treated clinical group(7 cows). The cows(treated clinical group) with fatty liver diagnosed before parturition were dosed with mixed compound of vitamin I(1head) and selenium(10mg/head) intramuscularly once before and after parturition, respectively. These cows(treated clinical group) were also given ursodeoxycholic acid(50g/head) intramuscularly 3 times before parturition. The cows(treated clinical group) with fatty liver diagnosed after parturition were also given the same compounds as dosed to the above cows at same dose rate once or 3 times, respectively after parturition. Blood samples were collected from the cows on 4th, 7th and 2nd day of preparturition and on 1st, 7th, 14th and 20th day of postparturition. Blood chemical values(non-esterified fatty acid : NEFA) concentration, serum aspartate aminotransferase activity, serum ${\gamma}$-glutamyl transpeptidase activity, bilirubin concentration, glucose level) were checked and clinical symptoms of the cows were also observed. 1. The cows in non-treated clinical group showed severe depression, anorexia and diarrhea from prepartum period, and retained palcenta, endometritis, ketosis, abomasal displacement and mastitis after parturition. Cows in treated clinical group showed moderate depression, anorexia, diarrhea during preparturient period, but they were relieved within a week from parturition. Cows in subclinical group showed mild depression, anorexia and diarrhea after parturition, but these symptoms were not observed in prepartum period. 2. NEFA concentration, serum aspartate aminotransferase activity, serum ${\gamma}$-glutamyl transpeptidase activity and bilirubin concentration observed In the cows of treated clinical group were significantly lower than those of the cows non-treated clinical group. The blood glucose concentration of the cows in treated clinical group were higher than those of the cows in non-treated clinical group. These results indicate that the preparturient and postparturient fatty liver of high-yielding dairy cows could be reduced by dosing the animals with appropriate amounts of mixed compound of vitamin I and selenium, and ursodeoxycholic acid at proper times of the preparturition and postparturition of the dairy cows.

• 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.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.8-14
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• 2023

The hepatic glycogen storage disease type 0 (GSD type 0) is an autosomal recessive disorder caused by a deficiency of hepatic glycogen synthase encoded by the glycogen synthase 2 (GYS2) gene, leading to abnormal synthesis glycogen. The clinical findings of GSD type 0 are hyperketotic hypoglycemia at fasting state and accompanying postprandial hyperglycemia and hyperlactatemia. GSD type 0 has only been reported in a very small number so far, and the diagnosis is likely to be missed because symptoms are mild, severe hypoglycemia is rare or asymptomatic, or symptoms gradually disappear with age. Essential management strategies include feeding high-protein meals to stimulate gluconeogenesis, frequent meals to prevent hypoglycemia during the day and feeding complex carbohydrates such as uncooked cornstarch to slowly release glucose during nignt. GSD type 0 has a good prognosis, with appropriate treatment, normal growth can be achieved and no complications occur. Significant hypoglycemia occurs less common in adulthood, but ongoing dietary management may be necessary.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.3
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• pp.96-102
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• 2017

Glycogen storage disease type IX (GSD IX) is caused by deficiency of phosphorylase kinase which plays a role in breakdown of glycogen. Mutations in PHKA2 are the most common cause of GSD IX (GSD IXa). Clinical manifestations of GSD IXa include hepatomegaly, elevation of liver enzyme, growth retardation, fasting hypoglycemia, and fasting ketosis. However, the symptoms overlap with those of other types of GSDs. Here, we report Korean familial cases with GSD IXa whose diagnosis was confirmed by targeted exome sequencing. A 4-year old male patient was presented with hepatomegaly and persistently elevated liver enzyme. Liver biopsy revealed swollen hepatocyte filled with glycogen storage, suggesting GSDs. Targeted exome sequencing was performed for the differential molecular diagnosis of various types of GSDs. A hemizygous mutation in PHKA2 were detected by targeted exome sequencing and confirmed by Sanger sequencing: c.3632C>T (p.Thr121Met), which was previously reported. The familial genetic analysis revealed that his mother was heterozygous carrier of c.3632C>T mutation and his 28-month old brother had hemizygous mutation. His brother also had hepatomegaly and elevated liver enzyme. The hypoglycemia was prevented by frequent meals with complex carbohydrate, as well as cornstarch supplements. Their growth and development is in normal range. We suggest that targeted exome sequencing could be a useful diagnostic tool for the genetically heterogeneous and clinically indistinguishable GSDs. A precise molecular diagnosis of GSD can provide appropriate therapy and genetic counseling for the family.