Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Juvenile visceral steatosis (JVS) mouse is an animal model of human primary carnitine deficiency caused by a mutation of the gene encoding carnitine transporter, and suffers from various symptoms, such as fatty liver, growth retardation, hyperammonemia, hypoglycemia, and cardiac hypertrophy. We have shown that hyperammonemia during the weaning period (15-26 days of age) is caused by suppression of urea cycle enzyme gene expression. The suppression resulted from activation of a transcription factor, AP-1. We have found that a cis-element for AP-1 binding is present in the enhancer region of the carbamoylphosphate synthetase (CPS) gene, and that the AP-1 binding site is involved in the suppression of CPS induction by dexamethasone in cultured hepatocytes and in the suppression of CPS expression in the liver of JVS mice. The blood ammonia levels in JVS mice increased during the weaning period, and then decreased to almost control levels after 30 days of age. In this paper, we report that in adult JVS mice, ammonia levels again increased after starvation for at least 24 hr and this effect was suppressed by carnitine treatment. Starvation for 48 hr did not significantly suppress CPS activity in the liver and did not cause any change in hepatic ornithine concentration. The concentration of N-acetylglutamate in the liver of starved JVS mice was not significantly different from that of JVS mice treated with carnitine. These results indicate that the hyperammonemia in carnitine-deficient adult JVS mice during starvation and the suppression by carnitine treatment differ from those found during the weaning period, and thus the cause of hyperammonemia and the mechanism of suppression remain to be solved.
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PMID:Hyperammonemia in carnitine-deficient adult JVS mice used by starvation. 1260 12

The prevalence of individual hereditary metabolic diseases is low, but together they constitute an important group in which pregnancy is of growing interest because patients more often reach adulthood and consider progeny. Hereditary metabolic diseases of the woman, such as hyperhomocystinemia or urea cycle defect, can present during or directly after pregnancy for the first time with thrombosis or coma, respectively. Other hereditary metabolic diseases of the woman, such as glycogen storage disease type I or III, can progress during pregnancy and may result in renal insufficiency or cardiomyopathy. Maternal hereditary metabolic diseases, such as poorly controlled hyperhomocystinemia or phenylketonuria, can deleteriously affect the foetus. Hereditary metabolic diseases of the foetus may have implications for the foetus itself, e.g., lysosomal storage diseases of the foetus may cause hydrops foetalis, cardiomyopathy, or foetal demise. In addition, hereditary defects of long chain fatty acid oxidation of the foetus may result in severe haemolysis and elevated liver enzymes and low platelets, or acute fatty liver of pregnancy in the mother.
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PMID:[Inherited metabolic diseases and pregnancy: consequences for mother and child]. 1262 77

Silymarin, a natural acknowledged hepatoprotector used in humans to treat liver diseases, has been tested in dairy cows during peripartum, a period during which animals are subject to subclinical fatty liver. Ten grams of silymarin (76% pure extract consisting in flavonolignans, taxifolin, and other trace compounds) per day, was administered as a water suspension by an oral drench to 15 cows from d 10 before expected calving to 15 d after calving. Milk production was measured, and colostrum, milk, and blood samples were analyzed during the experimental period. Treated animals showed the peak of milk production at 55 +/- 1.85 d after calving, 1 wk before the control group (62 +/- 3.27 d); the average peak production was 41.6 +/- 1.05 kg for the treated group vs. 39.1 +/- 1.44 kg for the control; the treated animals maintained a greater milk production than control cows throughout lactation (9922.1 +/- 215.7 vs. 9597.8 +/- 225.4 kg). Milk composition was unaffected by treatment. No silymarin residues were detected in colostrum and all milk samples. After calving, body condition score (BCS) decrease was greater for control compared with treated cows. Glucose, urea, triglycerides (TG), total cholesterol, beta-hydroxibutyrate (BHBA), and gamma-glutamyl transferase (GGT) in plasma were unaffected by treatment. Plasma nonesterified fatty acids (NEFA) on d-7 were higher in treated cows compared with the control group (741 vs. 181 micromol/L). From this evidence, it is possible to conclude that silymarin beneficially affected lactation performances and body condition of treated animals. Blood and milk parameters do not indicate any adverse effects of feeding this natural compound.
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PMID:Effects of silymarin, a natural hepatoprotector, in periparturient dairy cows. 1532 38

Glycerol can alleviate the symptoms of ketosis when delivered as an oral drench. The addition of glycerol to the diet would eliminate the need for restraining cows for drenching yet deliver a glucogenic substrate, alleviate the fatty liver-ketosis complex, and improve lactational performance. For this study, 21 multiparous and 9 primiparous Holstein cows blocked by parity and expected calving date were used in a randomized block design to evaluate the effects of feeding glycerol from 14 d prepartum to 21 d in milk (DIM). Treatments (kg/d dry matter basis) were 0.86 of cornstarch (control), 0.43 cornstarch + 0.43 glycerol (LG), or 0.86 glycerol (HG), topdressed and hand-mixed into the upper one-third of the daily ration. All cows were fed a common diet from 22 to 70 DIM. Prepartum dry matter intake (DMI) was greater for cows fed the control diet compared with LG or HG (13.3, 10.8, and 11.3 +/- 0.50 kg/d, respectively). Prepartum plasma glucose, insulin, beta-hydroxybutyrate, nonesterified fatty acids, and ruminal profiles were not affected by treatments. Rumen fluid collected postpartum from cows fed LG and HG had greater total volatile fatty acids, greater molar proportions of propionate, and a decreased ratio of acetate to propionate. Furthermore, concentrations of butyrate tended to be greater in rumens of cows fed LG and HG. Postpartum concentrations of glucose in plasma were greatest for cows fed the control diet relative to LG and HG (66.0 vs. 63.1 and 58.4 mg/dL, respectively) and decreased sharply at 21 DIM, after treatments ended, for cows fed HG (diet x day interaction). Body weight and condition loss, plasma nonesterified fatty acids, and liver lipids during the first 21 DIM were similar among treatments. Postpartum DMI was not affected by treatments; however, a tendency was observed for a diet x day interaction for body weight, as cows fed LG gained more body weight from 21 to 70 DIM relative to cows fed HG. Yield of energy-corrected milk during the first 70 DIM tended to be greatest for cows fed the control diet. The LG and HG diets decreased urea nitrogen concentrations in milk relative to controls. Based upon prepartum DMI and concentrations of glucose and beta-hydroxybutyrate in blood postpartum, feeding glycerol to dairy cows at the levels used in this experiment increased indicators used to gauge the degree of ketosis in dairy cattle.
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PMID:Feeding glycerol to transition dairy cows: effects on blood metabolites and lactation performance. 1554 83

Citrin, encoded by SLC25A13, is a liver-type mitochondrial aspartate-glutamate carrier (AGC), of which deficiency, in autosomal recessive trait, causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). NICCD patients have jaundice, hypoproteinemia, hypoglycemia, galactosemia, growth retardation, fatty liver and multiple aminoacidemia including citrulline, methionine, threonine and tyrosine. Some of the neonates who have experienced NICCD suffer from severe CTLN2 more than 10 years or several decades later. In CTLN2, neuropsychotic symptoms such as disorientation, aberrant behavior, coma and death are observed. Laboratory findings reveal hyperammonemia, citrullinemia, fatty liver and liver-specific decrease in a urea cycle enzyme, argininosuccinate synthetase (ASS). In some cases, hyperlipidemia, pancreatitis and hepatoma are accompanied with CTLN2. Citrin as a liver-type AGC plays a role in supplying aspartate to the cytosol for urea, protein and nucleotide synthesis by exchanging mitochondrial aspartate for cytosolic glutamate and proton, and transporting cytosolic NADH reducing equivalent to mitochondria as a member of malate aspartate shuttle essential for aerobic glycolysis. AGC is also important for gluconeogenesis from lactate. Although it is difficult to explain pathogenesis of the symptoms such as cholestasis in NICCD and liver-specific decrease of ASS protein in CTLN2 from the functions of the AGC, some are understandable by the loss of citrin functions. Many CTLN2 patients have been treated with a low protein and high carbohydrate diet and glycerol at the hyperammonemic coma. We argue that those treatments may result in fatty liver, hyperlipidemia, hyperammonemia and even death due to loss of the citrin functions. Loss of citrin first cause deficiency of aspartate in the cytosol, which results in an increase in cytosolic NADH/NAD(+) ratio and then activation of fatty acid synthesis pathway to compensate the aberrant ratio. This follows inhibition of fatty acid oxidation. The peculiar fondness for food of CTLN2 patients who like protein and dislike carbohydrate and sweets may be related to their metabolic requirements.
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PMID:Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier. 1619 99

The main objective of this study was to test the extent to which injecting glucagon subcutaneously for 14 d beginning at d 2 postpartum would prevent fatty liver development in transition dairy cows. Twenty-four multiparous Holstein cows were fed 6 kg of cracked corn in addition to their standard diet during the last 30 d of a dry period to induce postpartum development of fatty liver. Glucagon at either 7.5 or 15 mg/d or saline (control) was injected subcutaneously 3 times daily for 14 d beginning at d 2 postpartum. Glucagon at 15 mg/ d prevented liver triacylglycerol accumulation in postpartum dairy cows. Glucagon at 7.5 mg/d showed potential for fatty liver prevention. Glucagon increased concentration of plasma glucose and insulin and decreased plasma nonesterified fatty acid concentrations. No effects of glucagon were detected on plasma beta-hydroxybutyrate concentrations. Glucagon affected neither feed intake nor milk production. Moreover, milk composition was not altered by glucagon. Milk urea N concentrations decreased, and plasma urea N concentrations tended to decrease during glucagon administration, indicating that glucagon may improve protein use. Liver glycogen concentrations were not affected by glucagon. No significant differences in body condition scores were detected among treatments throughout the study. These results indicate that subcutaneous glucagon injections can prevent fatty liver in transition dairy cows without causing major production and metabolite disturbances.
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PMID:Prevention of fatty liver in transition dairy cows by subcutaneous injections of glucagon. 1660 24

The purpose of the study was to evaluate the effect of retained fetal membranes (RFM) on serum minerals and energy- and protein-related metabolites in dairy cows at a herd with a recent history of fatty liver syndrome. Forty-seven multiparous Holstein cows were selected during transition period. Nine cows had RFM longer than 24 h after calving. Blood samples were obtained on prepartum days 21 and 7 and postpartum days 7 and 21. We used repeated measure procedure of anova to evaluate the effect of RFM on serum metabolites. Cows with RFM had significantly higher concentrations of beta-hydroxybutyrate, non-esterified fatty acids and triglycerides after calving, but had lower concentrations of cholesterol during transition period. The concentrations of serum albumin and blood urea nitrogen were also significantly lower in RFM-affected cows than non-affected ones after parturition. Our results suggested that negative energy balance (NEB) postpartum was associated with RFM in dairy cattle. However, our findings did not reveal a cause and effect relationship with respect to the role of NEB as a possible risk factor for RFM.
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PMID:Metabolic changes in cows with or without retained fetal membranes in transition period. 1730 72

Liver grafts are frequently discarded due to steatosis. Steatotic livers can be classified as suboptimal and deteriorate rapidly during hypothermic static preservation, often resulting in graft nonfunction. Hypothermic machine perfusion (MP) has been introduced for preservation of donor livers instead of cold storage (CS), resulting in superior preservation outcomes. The aim of this study was to compare CS and MP for preservation of the steatotic donor rat liver. Liver steatosis was induced in male Wistar rats by a choline-methionine-deficient diet. After 24 hours hypothermic CS using the University of Wisconsin solution (UW) or MP using UW-Gluconate (UW-G), liver damage (liver enzymes, perfusate flow, and hyaluronic acid clearance) and liver function (bile production, ammonia clearance, urea production, oxygen consumption, adenosine triphosphate [ATP] levels) were assessed in an isolated perfused rat liver model. Furthermore, liver biopsies were visualized by hematoxylin and eosin staining. Animals developed 30 to 60% steatosis. Livers preserved by CS sustained significantly more damage as compared to MP. Bile production, ammonia clearance, urea production, oxygen consumption, and ATP levels were significantly higher after MP as compared to CS. These results were confirmed by histology. In conclusion, MP improves preservation results of the steatotic rat liver, as compared to CS.
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PMID:Preservation of steatotic livers: a comparison between cold storage and machine perfusion preservation. 1739 43

Citrin is the liver-type mitochondrial aspartate-glutamate carrier that participates in urea, protein, and nucleotide biosynthetic pathways by supplying aspartate from mitochondria to the cytosol. Citrin also plays a role in transporting cytosolic NADH reducing equivalents into mitochondria as a component of the malate-aspartate shuttle. In humans, loss-of-function mutations in the SLC25A13 gene encoding citrin cause both adult-onset type II citrullinemia and neonatal intrahepatic cholestasis, collectively referred to as human citrin deficiency. Citrin knock-out mice fail to display features of human citrin deficiency. Based on the hypothesis that an enhanced glycerol phosphate shuttle activity may be compensating for the loss of citrin function in the mouse, we have generated mice with a combined disruption of the genes for citrin and mitochondrial glycerol 3-phosphate dehydrogenase. The resulting double knock-out mice demonstrated citrullinemia, hyperammonemia that was further elevated by oral sucrose administration, hypoglycemia, and a fatty liver, all features of human citrin deficiency. An increased hepatic lactate/pyruvate ratio in the double knock-out mice compared with controls was also further elevated by the oral sucrose administration, suggesting that an altered cytosolic NADH/NAD(+) ratio is closely associated with the hyperammonemia observed. Microarray analyses identified over 100 genes that were differentially expressed in the double knock-out mice compared with wild-type controls, revealing genes potentially involved in compensatory or downstream effects of the combined mutations. Together, our data indicate that the more severe phenotype present in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice represents a more accurate model of human citrin deficiency than citrin knock-out mice.
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PMID:Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency. 1759 76

In this prospective study the impact of fatty liver and an impaired liver function on the treatment outcome of displacement of the abomasum (DA) was investigated. In a yearlong period, all cows suffering from DA submitted to the clinic were included in this study. All cows were clinically examined before surgery and a serum sample was taken to measure the following parameters: ASAT, bilirubin, urea. Liver biopsy was performed in all cows. Liver fat content was measured gravimetrically and concentrations of triglycerides were measured using a commercial test kit. Reposition of DA was done using the method by Dirksen. A total of 365 cows with DA entered the study, 326 (89.3%) suffered from LDA and 39 (10.7%) from RDA. RDA-cows had significantly (p = 0.002) more days in milk than LDA-cows. RDA-cows had significantly (p < 0.001) higher urea concentrations than LDA-cows. Bilirubin concentrations (p = 0.008) and liver fat content, triglyceride concentrations and the ratio of triglycerides to fat (TRI/FAT) (p < 0.001) were significantly higher in LDA-cows. The majority of LDA-cows showed at least a mild fatty liver. Comparing the cows with successful and failed treatment showed that ASAT-activity (p = 0.021), bilirubin concentration (p = 0.001), triglyceride concentration in liver and TRI/FAT (all p < 0.001) were significantly higher in the unsuccessfully treated cows. In RDA cows, significant differences between successfully and unsuccessfully treated cows were only seen in urea concentration (p = 0.004). ROC-analysis was performed to determine whether any parameter is suitable for a prediction of treatment outcome. In RDA-cows no threshold value was traceable for urea concentration. In LDA cows, TRI/FAT showed the best curve progression. The threshold value of 53.5 % had a sensitivity of 0.720 and a specificity of 0.700. LDA-cows exceeding this threshold had a 2.4 higher risk of an unsuccessful treatment. Due to the good overall treatment success (92.3 %) the positive predictive value for an unsuccessful or ineffective treatment was 0.368 only. The results of our study clearly show that impaired liver function plays an important role in the outcome of treatment of LDA but not RDA. In spite of this no laboratory parameter provides sufficient power to make a predictive statement of treatment outcome.
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PMID:The use biochemical and hepatic parameters to predict treatment outcome of dairy cows suffering from displacement of the abomasum. 1764 23


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