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

1. The changes in a number of metabolic measurements brought about by low-biotin diets associated with high and low incidences of fatty liver and kidney syndrome (FLKS) were studied in healthy 4-week-old broiler chicks. 2. Liver pyruvate carboxylase (pyruvate: CO2 ligase (ADP); EC 6.4.1.1) activity was low in birds fed on a diet causing a high incidence FLKS but the addition of fat or protein to this diet, to decrease the incidence of FLKS, increased enzyme activity. 3. Liver weights, blood lactate concentrations, plasma lactate dehydrogenase (L-lactate: NAD oxidoreductase; EC 1.1.1.27) activitvities and values for C16:1 : C18:0 fatty acid in liver, adipose tissue and plasma triglyceride were highest in birds fed on the high-FLKS diet and all measurements were negatively correlated with pyruvate carboxylase activity. 4. Birds with high plasma lactate dehydrogenase activity or triglyceride C16:1 : C18:0 values were the most likely to develop FLKS when fasted. 5. There was no evidence that increased liver weight was associated with increase activities of certain other liver enzymes. 6. It is concluded that FLKS occurs in birds with little or no hepatic gluconeogenic capacity via pyruvate carboxylase as a result of a dietary insufficiency of biotin but that the initiation of the syndrome in probably associated with the inhibition of other pathways of gluconeogenesis.
 ...
PMID:Metabolic changes associated with the occurrence of fatty liver and kidney syndrome in chicks. 69 61

The effect of dietary orotic acid on the levels of liver and blood NAD in young rats was investigated. Weanling rats were fed on a nicotinic acid-free, 20% casein diet containing 0% (control diet) or 1% orotic acid (test diet) for 32 days. Retardation of growth, development of fatty liver and enlargement of liver were observed in the test group in comparison with the control group. In the test group, the amounts of quinolinic acid, niacin, NAD and N1-methylnicotinamide, and the activities of quinolinate phosphoribosyltransferase, nicotinamide mononucleotide adenylyltransferase, nicotinamide methyltransferase and NAD synthetase expressed in terms of g liver were significantly decreased compared to the control group. When these values were expressed in terms of whole liver, a significant difference was observed in the content of NAD and the activity of NAD synthetase between the control and the test groups. The activity of aminocarboxymuconate-semialdehyde decarboxylase expressed in terms of whole liver was about 2-fold higher in the test group than in the control group, but was not significantly different. The levels of NAD in blood as well as in liver were significantly lower in the test group than in the control group. Urinary excretions of quinolinic acid, niacin and N1-methylnicotinamide were also reduced in the test group. These results are discussed in the light of the reported effect of orotic acid in lowering the level of ATP in liver.
 ...
PMID:Effect of dietary orotic acid on the levels of liver and blood NAD in rats. 293 93

The sulphur-containing drug, di-isopropyl-1,3-dithiol-2-ylidenemalonate (Malotilate) protects against the increase in hepatic triglyceride concentration after acute ethanol administration (either 6 g/kg p.o. or 2 g/kg i.p.) in rats. The compound had no influence on the increased hepatic NADH:NAD ratio (measured as the lactate:pyruvate and 3-hydroxybutyrate:acetoacetate ratios) after acute ethanol dosing (2 g/kg i.p.), but was found to lower hepatic acetaldehyde concentrations and prevent some of the disturbances in lipid metabolism observed in liver slices from ethanol-treated animals (e.g. decreased oxidation of [1-14C]palmitate to 14CO2) after this ethanol dose. The drug did not inhibit ethanol metabolism in this acute experiment. Administration of Malotilate to Wistar rats (100 mg/kg/day orally) during chronic feeding of ethanol as 36% of the total calorie intake in a liquid diet, resulted in a lower intake of the alcohol-containing diet by ethanol-fed animals and reduced body weight gain in rats which received the drug, without blood ethanol levels or the ethanol intake (expressed in g/kg body weight/day) being affected. In ethanol-fed animals, Malotilate prevented the production of fatty liver and the adaptive increase in the ethanol elimination rate (EER) normally seen in ethanol-fed animals, although the drug actually caused a slight increase in EER in glucose pair-fed controls. Malotilate did not significantly decrease the degree of induction of microsomal cytochrome P-450 by ethanol, but the increase in aniline hydroxylation was much less marked in animals receiving ethanol and Malotilate, suggesting that the activity of the inducible microsomal ethanol oxidising system (MEOS) may be reduced by the compound. Determination of hepatic acetaldehyde concentrations during ethanol feeding, and during an acute ethanol challenge test following long-term ethanol treatment showed that the compound significantly lowered the level of this ethanol metabolite in the liver under both circumstances. This reduction of hepatic acetaldehyde concentrations, probably resulting in part from the reduced EER as well as increased low-Km aldehyde dehydrogenase activities and glutathione contents seen in the livers of Malotilate-treated rats, are possible mechanisms by which the drug protects against triglyceride accumulation after ethanol administration.
 ...
PMID:The effect of di-isopropyl 1,3 dithiol-2-ylidenemalonate (malotilate) on the hepatic changes induced by ethanol administration in the rat. 314 67

The conversion of xanthine dehydrogenase to xanthine oxidase that produces oxygen radicals has been implicated in the ischemic injury to the myocardium and to the kidney. Xanthine dehydrogenase uses NAD as the electron acceptor to catalyze a reaction which does not produce any oxygen free radicals and may depress the conversion of xanthine dehydrogenase to xanthine oxidase. Nicotinamide is the preferred precursor for NAD. This study was conducted to examine the effect of an 18% casein diet supplemented with 0.5% nicotinamide on the activity of oxidoreductase and its two enzyme forms, xanthine dehydrogenase and xanthine oxidase, in kidney, heart and liver of female obese Zucker rats that spontaneously develop glomerulosclerosis, cardiomegaly and fatty liver. Lean litter mates were used as controls. Nicotinamide supplementation had no effect on the activities of these enzyme forms in the liver of either obese rats or lean rats. Obese rats fed the nicotinamide supplemented diet had higher activities of these enzyme forms in kidneys and hearts than unsupplemented diet fed obese rats, but this difference was not observed in lean rats. In unsupplemented rats, xanthine oxidase activity in the kidney was greater in lean rats than obese rats. Thus, the abnormalities observed in obese rats are unlikely attributable to the xanthine oxidase-mediated oxidant stress.
 ...
PMID:Dietary nicotinamide supplementation increases xanthine oxidoreductase activity in the kidney and heart but not liver of obese Zucker rats. 761 99

Oxidative stress in the course of diabetes mellitus can cause disturbance of lipid membranes of cellular organelles. The study is aimed at the determination of oxidative phosphorylation in mitochondria in rats with experimentally induced acute and chronic insulin-dependent diabetes mellitus (IDDM). IDDM was induced by single dose of streptozotocin (45 mg per kg-1). Insulin Interdep (6 U per kg-1) was administered once a day subcutaneously. The authors investigated glycaemia, cholesterol and triacylglycerol concentrations in the blood and liver. Isolation of mitochondria was succeeded by measurement of oxidative phosphorylation indicators after 8 days (acute IDDM) or after 8 weeks (chronic IDDM) from streptozotocin administration. The authors found out that both acute and chronic IDDM were concommited by hyperglycaemia. The group with acute IDDM yielded an increase in cholesterol and triacyglycerols concentrations in the blood, as well as that of cholesterol in the liver. The group with chronic IDDM yields an increase in cholesterol in the blood. Trialcylglycerols in the liver increased in none of the investigated groups. Liver steatosis did not occur. Indicators of oxidative phosphorylation in the liver mitochondria of rats with acute and with chronic IDDM decreased in contrast to healthy controls from NAD substrates glutamate and pyruvate and also form FAD substrate of succinate. Significant decrease in consumption of oxygen in the 3 state occurred, while in acute IDDM the decrease was more significant than in chronic IDDM. Phosphorylation rate significantly decreased in contrast to controls, but there was no difference between IDDM groups. The investigation results imply that in both acute and chronic IDDM there are decreased effectivity of energetic metabolism in liver mitochondria. (Tab. 5, Ref. 29.).
 ...
PMID:[Bioenergetics of liver mitochondria in rats in experimental insulin-dependent diabetes]. 901 45

The extensive role of the microsomal mixed-function oxidase (MFO) system in the oxidation of endo-and xenobiotics, in the detoxication, in the generation of reactive free radicals and in the decomposition of the end products of lipid peroxides is well documented in the literature. Steatotic liver is a very frequent damage with different etiology. Drug metabolising reactions are suppressed in fatty liver, in which pathologically increased production of reactive oxygen intermediates may lead to the peroxidation of microsomal membrane lipids and to the change of membrane bound enzyme activities because of overwhelmed protective mechanisms. The subnormal activity of the MFO system may diminish the non specific resistance of the organism. Therefore we have studied the effects of natural flavonoids and polyphenolic compounds on the mixed-function oxidases. Antioxidant, O(2)(-&z.rad;) and &z. rad;OH scavenger properties of Sempervivum tectorum extract (STF1) were proved by EPR spectroscopic and chemiluminometric techniques. Potential bioactive constituents were determined by chromatography (HPLC, TLC) and spectrometric (UV, UV-VIS) methods. In the present study we reflect on the membrane stabilising, antioxidant and lipid metabolism modifying effects of this extract. It was established that activities of NAD(P)H reductase and content of cytochrome P450 were normalised in liver microsomes of hyperlipidemic rats, if the animals were treated with STF1 (2 g/bwkg for 9 days in drinking water parallel with fat-rich diet feeding). Fatty acid composition, examined by HRGLC analysis, was changed beneficially. NADPH induced lipid peroxidation was also decreased in microsomes in in vivo and in vitro experiments. At the same time the STF1 had no significant influence on MFO system in normolipidemic animals and on cytochrome b5 concentration of microsome fractions of hyperlipidemic rats.
 ...
PMID:Membrane stabilising effects of natural polyphenols and flavonoids from Sempervivum tectorum on hepatic microsomal mixed-function oxidase system in hyperlipidemic rats. 1109 Oct 2

The effects of dietary orotic acid on the metabolism of tryptophan to niacin in weaning rats was investigated. The rats were fed with a niacin-free, 20% casein diet containing 0% (control diet) or 1% orotic acid diet (test diet) for 29 d. Retardation of growth, development of fatty liver, and enlargement of liver were observed in the test group in comparison with the control group. The concentrations of NAD and NADP in liver significantly decreased, while these in blood did not decrease compared to the control group. The formation of the upper metabolites of tryptophan to niacin such as anthranilic acid, kynurenic acid, and 3-hydroxyanthranilic acid were not affected, but the quinolinic acid and beyond, such as nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide, were significantly reduced by the administration of orotic acid. Therefore, the conversion ratio of tryptophan to niacin significantly decreased in the test group in comparison with the control group.
 ...
PMID:Effects of fatty liver induced by niacin-free diet with orotic acid on the metabolism of tryptophan to niacin in rats. 1216 38

Alcohol has long been thought to cause fatty liver by way of altered NADH/NAD(+) redox potential in the liver, which, in turn, inhibits fatty acid oxidation and the activity of tricarboxylic acid cycle reactions. More recent studies indicate that additional effects of ethanol both impair fat oxidation and stimulate lipogenesis. Ethanol interferes with DNA binding and transcription-activating properties of peroxisome proliferator-activated receptor-alpha (PPARalpha), as demonstrated with cultured cells and in ethanol-fed mice. Treatment of ethanol-fed mice with a PPARalpha agonist can reverse fatty liver even in the face of continued ethanol consumption. Ethanol also activated sterol regulatory element binding protein 1, inducing a battery of lipogenic enzymes. These effects may be due in part to inhibition of AMP-dependent protein kinase, reduction in plasma adiponectin, or increased levels of TNF-alpha in the liver. The understanding of these ethanol effects provides new therapeutic targets to reverse alcoholic fatty liver.
 ...
PMID:Recent advances in alcoholic liver disease II. Minireview: molecular mechanisms of alcoholic fatty liver. 1519 57

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.
 ...
PMID:Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier. 1619 99

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.
 ...
PMID:Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency. 1759 76


1 2 3 4 5 6 7 8 Next >>