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)

Changes of enzymes involved in the hepatic metabolism of long-chain fatty acids (palmitoyl-CoA synthetase (EC 6.2.1.3), carnitine palmitoyltransferase (EC 6.2.1.3), glycerophosphate acyltransferase (EC 2.3.1.15)) in the liver of male rats were examined after ethionine exposure. Ethionine administration resulted in a dose- and time-dependent enhancement of the palmitoyl-CoA synthetase activity both in the mitochondrial, peroxisomal and microsomal fractions. The total carnitine palmitoyltransferase activity in the mitochondrial fraction was enhanced. Ethionine administration was also associated with dose- and time-dependent changes of the microsomal glycerophosphate acyltransferase activity, whereas the mitochondrial enzyme activity was marginally affected. The hepatic triacylglycerol content of the ethionine-treated animals was increased. Hepatic lipids were accumulated in large droplets. Serum triacylglycerol and cholesterol were decreased. In particular, the serum HDL-cholesterol level was lowered. The concentration of ATP in the liver decreased. Accumulation of the metabolic product S-adenosylethionine (AdoEth) was observed for the first 2 days of exposure followed by a fall in S-adenosylmethionine (Ado-Met) during the next 10 days. Linear regression analysis of ATP content versus AdoEth and AdoMet showed highly significant correlations. A significant correlation between the hepatic triacylglycerol and AdoEth content was also observed upon ethionine treatment. The data show that ethionine perturbs the hepatic lipid metabolism. Enhanced esterification of long-chain fatty acids, but not a simple reduction of their oxidation, might contribute to ethionine-induced fatty liver in addition to a block in secretion of lipoproteins and decreased protein synthesis.
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PMID:Ethionine-induced alterations of enzymes involved in lipid metabolism and their possible relationship to induction of fatty liver. 297 12

The activities of three enzymes catalyzing the production or degradation of phosphatidylcholine, a major structural phospholipid of cell membranes, were assessed in hepatocyte membrane microsomal preparation from patients with various types of liver disease. Choline phosphotransferase activity of preparation from patients with chronic aggressive, chronic active, chronic persistent, alcoholic hepatitis and cirrhosis accompanied by marked necrosis and relatively slight fibrosis was markedly decreased, compared with normal liver; the activity from patients with fatty liver and chronic inactive hepatitis was slightly decreased. Specimens from patients with acute transient hepatitis were not significantly different from normal. Methyltransferase and phospholipase A2 activities tended to parallel that of choline phosphotransferase, although the degree of changes was generally less marked. Our studies indicate that enzyme activities that are critical for hepatic cell membrane integrity and activity are attenuated in liver specimens from patients with disease in which there is marked hepatic cell necrosis.
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PMID:Phospholipid transmethylation and choline phosphotransferase in microsomal fraction of human diseased liver. 301 86

In liver biopsy material of eighty-nine patients with suspected liver disease the drug-metabolizing function was investigated. The capacity of the liver to oxidatively metabolize drugs was assessed by determination of cytochrome P-450 dependent monooxygenase activity in vitro. The biotransformational function of these microsomal enzymes was tested with compounds representing the activity of oxidative drug metabolism (7-ethoxycoumarin, p-nitroanisol and cytochrome c). From the eight-nine patients sixty-one had various liver diseases not related to ethanol and twenty-eight abused ethanol. When both groups were matched for age, sex, smoking, treatment with sedatives, drugs and degree of liver damage the alcoholic group had significantly higher activities of 7-ethoxycoumarin O-deethylase (EOD: 76.9 +/- 31.1 pmol min-1 mg-1 protein, mean +/- SD) than the non-alcoholic liver disease group (42.7 +/- 14.1). The inducing effect of ethanol was most striking on the EOD activity, less for the O-demethylation of p-nitroanisol (PNA) and not present for the NADPH-cytochrome c reductase. The induced patients were analysed in detail to find out which factors were responsible for the observed scatter of enzyme activities within the alcoholic group. Alcoholics with fatty liver (n = 7) had the highest EOD activities (108.9 +/- 25.0), patients with alcoholic hepatitis (n = 10) had significantly less activity (66.0 +/- 1.9) than the former group. However, alcoholics without liver damage (n = 6) had activities not significantly different (46.0 +/- 15.8) from controls (39.4 +/- 9.1). These subgroups among the alcoholics were comparable in terms of sex, age, smoking and drinking habits.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inducing efficacy of ethanol on hepatic drug metabolizing enzymes in patients. 309 41

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.
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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

Chronic ethanol consumption results in the induction of a specific hepatic cytochrome P-450 (P450IIE1). However, since compounds other than ethanol (i.e., acetone) can also serve as P450IIE1 inducers, and since ethanol given with a normal fat-containing (35% of energy) diet is associated with acetonemia, hepatic steatosis and decreased body weight gain, the question has been raised whether induction is mediated specifically by ethanol or whether it might represent a nonspecific response to these other factors. This was investigated by varying both the mode of ethanol administration and the composition of the diet. By administering ethanol in the drinking water, or as part of a low-fat (5% of energy) liquid diet, a significant induction of P450IIE1 and of the activities of the microsomal ethanol oxidizing system and p-nitrophenol hydroxylase was demonstrated in the absence of any significant increase in blood acetone with minimal increase in liver total lipids. Induction of P450IIE1 was comparable with the low or normal fat-containing diets, but MEOS activity rose more with the latter, possibly reflecting a potentiating effect of dietary fat on ethanol oxidation by P-450 enzymes other than P450IIE1. When the lack of weight gain of the alcohol fed animals was mimicked in controls by decreasing the amount of diet ingested, no induction was observed. Varying the pattern of liquid diet feeding had no demonstrable differential effect. Thus, the induction of P450IIE1 after chronic ethanol consumption can be attributed to ethanol itself, but dietary fat can potentiate the induction of the microsomal ethanol oxidizing system and of p-nitrophenol hydroxylase.
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PMID:Role of acetone, dietary fat and total energy intake in induction of hepatic microsomal ethanol oxidizing system. 318 73

Hepatic steatosis was induced in rats by feeding nutritionally adequate liquid diet containing ethanol as 36% of energy for 4-5 weeks. After 24 h fasting and withdrawal from ethanol, liver ischaemia for 30 min followed by 2 h reperfusion resulted in a significant increase in microsomal lipid peroxide content and a decrease in reduced glutathione content as well as in protein synthesis with a rapid accumulation of triglyceride in the liver. In rats fed a non-ethanol diet or those fed a high-cholesterol diet with hepatic steatosis, however, similar phenomena were not found. These findings suggest that chronic ethanol feeding potentiates hepatic lipid peroxidation.
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PMID:Evidence for potentiation of lipid peroxidation in the rat liver after chronic ethanol feeding. 320 Oct 94

Trifluoperazine (TFP) (50 mg/kg ip) administration to rats 6 or 10 hr after CCl4 (1 ml/kg ip in olive oil) significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as evidenced by either histology or electron microscopy. TFP given 6 hr after CCl4 significantly decreased the CCl4-induced increases in liver calcium content. TFP raised four to five times the liver glycogen content in control rats but was unable to modify decreased glycogen content of CCl4 poisoned animals. TFP administration increased phospholipid and protein synthesis as evidenced by studies on 32P incorporation into microsomal phospholipid and by experiments on [14C]leucine incorporation in microsomal protein fractions from control rat livers. No significant changes were observed in microsomal phospholipid degradation as studied by decay of label from 32P-prelabeled microsomal lipids or in increased protein degradation as evidenced by decay of label from [14C-guanidino]arginine-prelabeled microsomal proteins found in livers of control rats after TFP treatment. Electron microscopy observations of liver from control animals treated with TFP evidenced accumulation of glycogen in areas close to smooth endoplasmic reticulum (SER); large Golgi areas with an abundant number of lysosomes, and minor dilatation effects on the rough endoplasmic reticulum (RER) and nuclear membrane. Results suggest that TFP preventive effects might be due to the anticalmodulin actions of this drug.
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PMID:Further studies on the late preventive effects of the anticalmodulin trifluoperazine on carbon tetrachloride-induced liver necrosis. 337 54

1. Changes in lipid content and composition of liver and bile during pre- and post-laying periods were investigated in hens of a laying strain. 2. The large increase in liver lipid concentration, particularly triacylglycerols, at the onset of laying was accompanied by the appearance of triacylglycerols in the bile. 3. Accumulation of triacylglycerol in the liver was increased by a diet containing maize and soyabean meal. This was associated with increases in the triacylglycerol concentration in both serum and bile. 4. Liver microsomal phosphatidate phosphohydrolase activity was positively correlated with liver triacylglycerol content in birds given the maize/soyabean meal diet. 5. The time course of triacylglycerol accumulation in the liver and associated changes in the bile triacylglycerol concentration in laying strain hens were different to those previously observed in broiler hens. 6. Over the lifetime of the bird, secretion of triacylglycerols into bile may play an important role in the prevention of fatty liver syndromes.
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PMID:Effects of age and diet on the lipid content and composition of gallbladder bile, liver and serum in laying strains of hen. 344 28

The role of the liver in glucose metabolism was investigated in 24 consecutive patients undergoing diagnostic liver biopsy by comparing hepatic morphometry and microsomal enzyme activity in vivo (antipyrine) with fasting blood glucose (BG) and immunoreactive insulin (IRI) levels and with the metabolic clearance rate of insulin and the insulin sensitivity index. The patients had elevated BG and IRI levels and reduced insulin-mediated glucose metabolism, insulin sensitivity index, and microsomal enzyme activity as compared with controls. The insulin metabolic clearance rate did not diverge among the groups. Patients with fatty liver had a high BG associated with a reduced glucose disposal rate, whereas fasting IRI did not diverge when compared with other liver patients. Glucose disposal rate was related to the amount of unaltered liver (r2 = 0.640; p less than 0.001) and antipyrine metabolism (r = 0.631; p less than 0.01) and inversely related to the amount of fat (r2 = 0.585; p less than 0.01). The findings demonstrate that insulin-mediated glucose metabolism is related to liver structure and microsomal function. Accumulation of fat in the liver seems to be a major factor associated with reduced insulin sensitivity and glucose tolerance.
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PMID:Insulin-mediated glucose metabolism is related to liver structure and microsomal function. 352 63

The pathogenetic role of lipid peroxidation in ethanol-induced liver injury was previously supported by demonstration of increased formation of diene conjugates and decreased hepatic levels of reduced glutathione in ethanol-fed animals and alcoholic patients with liver injury. The present study was carried out to investigate whether these findings can be extended to a rat model that was shown to produce a spontaneous ethanol-induced liver injury progressing from steatosis to necrosis and fibrosis (Hepatology 6: 814, 1986). Despite the histological evidence of progression from hepatic steatosis to centrilobular necrosis in these animals, diene conjugate formation in mitochondrial and microsomal lipids was not enhanced when compared to pair-fed controls. In addition, hepatic levels of neither methionine nor glutathione were decreased in the ethanol-fed animals. The fatty acid composition of mitochondrial phospholipids from these animals was similar to that in the controls. However, in the microsomal phospholipids, the level of arachidonate (20:4) was depressed by about 50% as compared to the controls. These results demonstrate the lack of evidence for a pathogenetic relationship between lipid peroxidation and ethanol-induced liver injury progressing to centrilobular necrosis. They further suggest that the decreased levels of 20:4 commonly seen after chronic ethanol intake may not be due to a peroxidative loss.
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PMID:Lack of evidence for increased lipid peroxidation in ethanol-induced centrilobular necrosis of rat liver. 368 96


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