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)

An experimental model for monitoring rat liver function during protracted exposure to hepatotoxic agents is proposed. Owing to their invasiveness, the models usually employed are appropriate for studying the mechanism of action of toxic substances, but do not allow the liver situation to be followed over the course of time. The need to sacrifice animals to determine liver triglycerides-one of the key parameters in the progress of toxic damage- reduces the possibility of following such progress in the same animals. This study describes the testing of a model for monitoring three basic parameters of liver injury: cytolysis, steatosis and metabolic deficiency of the liver. CCl4 has been chosen as model-hepatotoxin. Steatosis is determined by evaluating the triglyceride content of small specimens of liver, obtained through open-field biopsies, which appear to be representative of the whole liver. Fatty liver is paralleled by the block in Triton-induced hypertriglyceridaemia. Determination of serum triglycerides derives from a very poorly invasive technique which can be repeated several times. The combination of these tests with the assessment of both the cytolysis (ALT and SDH release into the circulation) and the impairment of the efficiency of liver microsomal enzymes (TMO clearance), seems to offer a reliable experimental procedure in predicting the hepatotoxic effect of xenobiotics.
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PMID:A model for monitoring changes in liver function. 379 13

The relationship between hepatic glycerolipids and microsomal drug-metabolizing enzymes was studied in liver biopsies from 41 subjects. The series included obese, diabetic, epileptic and chronic alcoholic patients, all of whom were hospitalized for suspected hepatic ailments (fatty liver, hepatitis or cirrhosis). Therapy with enzyme-inducing anticonvulsants was associated with high phospholipid and cytochrome P-450 and low triacylglycerol concentration in the liver. In patients with fatty liver or cirrhosis low phospholipid and cytochrome P-450 and high triacylglycerol concentrations were observed. There was a significant correlation (r (Pearson's product moment correlation coefficient) = 0.91) between the hepatic phospholipid and cytochrome P-450 concentration. The cytochrome P-450 concentration was inversely related (r = -0.74) to the triacylglycerol concentration. The positive correlation between hepatic phospholipids and drug-metabolizing enzymes could be interpreted as indicating that in human liver phospholipid and cytochrome P-450 synthesis share common regulators, or that phospholipids are necessary for the maximum rate of cytochrome P-450 synthesis.
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PMID:Relationship between lipid composition and drug metabolizing capacity of human liver. 398 78

A high cholesterol diet induced a fatty liver and an increase in cholesterol oleate in spontaneously hypertensive rats. The activity of microsomal glycerophosphate acyltransferase in liver increased 2-3-fold to meet the increased supply of oleate, the synthesis of which was stimulated by a 10-fold increase in microsomal delta 9-desaturase activity. Hepatic fatty acid synthetase and diacylglycerol acyltransferase activities were decreased somewhat. These results, together with the fact that the large increases in hepatic cholesterol ester and triacylglycerol were not correspondingly reflected in plasma, indicated that the fatty liver resulted from decreased secretion of lipoprotein rather than increased lipogenesis. Endogenous cholesterol in liver microsomes increased 2-fold and hepatic acyl-CoA:cholesterol acyltransferase activity increased 3-fold, whereas plasma lecithin:cholesterol acyltransferase activity was unchanged. Thus, the increase in cholesterol oleate seen in spontaneously hypertensive rats fed a high cholesterol diet is due mainly to increases in acyl-CoA:cholesterol acyltransferase and delta 9-desaturase activities.
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PMID:Effect of a high cholesterol diet on lipid metabolizing enzymes in spontaneously hypertensive rats. 405 45

Early effects of choline deficiency were studied in rats. Nonphospholipid ("neutral lipid") and phospholipid were measured in plasma and in three fractions of a liver homogenate: sediment, supernatant fraction, and "floating fat." A single choline-deficient meal caused significant aberrations from the typical diurnal changes observed in the lipid fractions of the controls. These changes occurred in the following sequence: (a) failure of phospholipid to increase, after feeding, in the sediment fraction; (b) increase of neutral lipid, compared with controls, exclusively in the floating fraction; and (c) failure of neutral lipid to return to control levels. The rate of accumulation of neutral lipid increased during the first 4 days of deficiency. The occurrence of NADH-cytochrome c dehydrogenase in the floating fat and the absence of succinate dehydrogenase activity point to microsomal origin of the floating fat. Early effects of choline deficiency on plasma lipids were limited to phospholipid, and occurred later than changes in the liver. Plasma nonphospholipid levels were unchanged during the first 2 days; this does not support impaired secretion or transportation of glyceride as the cause of fatty liver in the early stages of choline deficiency.
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PMID:Diurnal changes in liver and plasma lipids of choline-deficient rats. 590 Feb 9

Replacement of dietary triglycerides containing long-chain fatty acids (LCFA) by triglycerides containing medium-chain fatty acids (MCFA) markedly reduced the capacity of alcohol to produce fatty liver in rats. After 24 days of ethanol and MCFA, the increase in hepatic triglycerides was only 3 times that of controls, whereas an 8-fold rise was observed after ethanol and LCFA. The triglyceride fatty acids that accumulated in the liver after feeding of ethanol with MCFA contained only a small percentage of the MCFA; their composition also differed strikingly from that of adipose lipids. To study the mechanism of the reduction in steatosis, we compared oxidation to CO(2) and incorporation into esterified lipids of (14)C-labeled chylomicrons or palmitate-(14)C (representing LCFA), and of octanoate-(14)C (as MCFA) in liver slices and isolated perfused livers, in the presence or absence of ethanol. Ethanol depressed the oxidation of all substrates to CO(2); MCFA, however, was much more oxidized and reciprocally much less esterified than LCFA, with a 100-fold difference in the ratio of esterified lipid-(14)C to (14)CO(2). Furthermore, in hepatic microsomal fractions incubated with alpha-glycerophosphate, octanoate was much less esterified than palmitate. This propensity of MCFA to oxidation rather than esterification represents a likely explanation for the reduction in alcoholic steatosis upon replacement of dietary LCFA by MCFA.
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PMID:Difference in hepatic metabolism of long- and medium-chain fatty acids: the role of fatty acid chain length in the production of the alcoholic fatty liver. 603 39

Four Macaca fascicularis monkeys were maintained 1 year on a liquid diet containing 26% of calories as ethanol. Four control animals were fed a liquid diet of equivalent calories with protein, carbohydrate, and fat being substituted for ethanol calories. In liver mitochondria prepared from ethanol-fed monkeys (ethanol mitochondria), respiratory control was lowered 20% due to a decrease in state 3 respiration (28%). This was also accompanied by a 20% decrease in ADP translocation into ethanol mitochondria. The major change was a 61% decrease in cytochrome oxidase activity. The respiratory rate in the presence of uncoupler was also lowered 14%, but the decrease was not statistically significant. In contrast with our earlier observations with Macaca nemestrina, no significant ethanol-induced changes were observed in enzyme activities associated with the microsomal electron transport system, and no ethanol-elicited fatty liver was evident. The major changes in fatty acid composition of microsomal and mitochondrial phospholipids were increased amounts of palmitoleic and oleic acids, and decreased amounts of linoleic and arachidonic acids.
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PMID:Ethanol-related changes in liver microsomes and mitochondria from the monkey, Macaca fascicularis. 641 31

Hepatic steatosis frequently complicates total parenteral nutrition (TPN). Some of the mechanisms responsible were examined in rats receiving calories as dextrose (CHO-TPN) or dextrose plus lipid emulsion (Lipid-TPN). Hepatic triglyceride content increased approximately threefold after CHO-TPN and twofold after Lipid-TPN (P less than 0.02). Hepatic triglyceride fatty acid composition reflected endogenous synthesis. Hepatic acetyl-Coenzyme A carboxylase specific activity increased fourfold after CHO-TPN and twofold after Lipid-TPN, and it correlated positively with hepatic lipid content (r = 0.82). The activities of the microsomal enzymes of complex lipid synthesis were unchanged in the TPN groups. Both TPN regimens suppressed hepatic triglyceride secretion, measured by the rise in plasma triglyceride and the incorporation of [14C]palmitic acid into plasma triglyceride after intravenous Triton. Hepatic triglyceride secretion correlated negatively with total hepatic lipid content (r = -0.89). CHO-TPN increased the uptake of a radiolabeled triglyceride emulsion and increased hepatic lipase activity, whereas Lipid-TPN decreased both. Both adipose and cardiac lipase were higher for Lipid-TPN animals than for CHO-TPN or control animals. Hepatic 14C-triglyceride content was increased in both TPN groups as compared with controls after the injection of 1-[14C]-palmitic acid. This increment was proportional to the decreased hepatic secretion. Triglyceride fatty acid oxidation was significantly suppressed by CHO-TPN, less so by Lipid-TPN. Free fatty acid oxidation was suppressed only by CHO-TPN. The results suggest that the steatosis induced by TPN in rats was due to enhanced hepatic synthesis of fatty acid and reduced triglyceride secretion. Reduced hepatic triglyceride uptake, enhanced fatty acid oxidation, and enhanced peripheral tissue plasma triglyceride lipolysis when CHO-TPN is supplemented with lipid may modulate the accumulation of hepatic triglyceride and, along with reduced synthesis of fatty acid, lead to a lower hepatic triglyceride content.
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PMID:Pathogenesis of hepatic steatosis in the parenterally fed rat. 643 55

To study the effects of alcoholic liver injury on the ability of ethanol to promote hepatic fat accumulation and hyperlipemia, baboons were pair-fed liquid diets containing 50% of energy either as ethanol or as additional carbohydrate (controls) for 1 to 7 years. Alcohol consumption produced triacylglycerol accumulation in the liver, hypertriacylglyceridemia, and various degrees of liver injury, including cirrhosis. At the early stages of fatty liver (with or without perivenular fibrosis), there was increased activity of microsomal diacylglycerol acyltransferase and of both microsomal and cytosolic phosphatidate phosphohydrolase, with no changes in glycerol-3-phosphate acyltransferase. With progression of the liver injury and development of septal fibrosis and/or cirrhosis, the rate of hepatic triacylglycerol accumulation and the magnitude of the hyperlipemia decreased, despite continuous ethanol intake. These changes were associated with disappearance of the increases in microsomal diacylglycerol acyltransferase and cytosolic phosphatidate phosphohydrolase activities, whereas those of microsomal phosphatidate phosphohydrolase remained elevated and glycerol-3-phosphate acyltransferase was unaffected. Thus, changes in the activity of two enzymes of the triacylglycerol-synthesizing pathway, namely the microsomal diacylglycerol acyltransferase and the cytosolic phosphatidate phosphohydrolase, may contribute to the differences in the rate of hepatic triacylglycerol accumulation and the degree of hyperlipemia during progression of the alcoholic liver damage.
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PMID:Hepatic triacylglycerol synthesizing activity during progression of alcoholic liver injury in the baboon. 649 27

Three experiments were conducted to investigate the effect of diet and estradiol (E2) administration on hepatic microsomal mixed function oxidase (MFO) activity, E2 metabolism, and liver lipid content in male broiler chicks. Broiler chicks (3 weeks of age) were fed either a corn-soybean (CS) diet or a diet containing fish meal, alfalfa meal, and torula yeast (FAY) for 19 days in Experiments 1 and 3 and for 14 days in Experiment 2, respectively. Half of the chicks were implanted with tubes containing E2. In all experiments when the chicks were estrogenized, feeding FAY significantly lowered liver lipid content and plasma E2 concentration. Activity of hepatic microsomal aniline hydroxylase and content of cytochrome P-450 were significantly increased by feeding FAY with or without E2 administration. The chicks fed the CS diet had a significantly lower content of cytochrome P-450 when E2 was administered. Activities of aminopyrine demethylase and nicotinamide adenine dinucleotide phosphate, reduced (NADPH)-cytochrome C reductase did not differ significantly between the diets. In in vitro studies, conversion of 14C-E2 into the water soluble fraction was significantly increased in microsomes from chicks fed the FAY diet as compared to ones from chicks fed the CS diet. The results suggest that some of the hepatic microsomal functions on the CS diet are modified by the change in diet composition and that these modifications are probably associated with E2 metabolism and occurrence of fatty liver.
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PMID:Effect of dietary composition and estradiol implants on hepatic microsomal mixed function oxidase and lipid deposition in growing chicks. 651 66

The relationship between blood lactate levels, liver histology and microsomal enzyme activity (cytochrome P-450 content) was assessed in 32 non-insulin-dependent diabetics (NIDD) undergoing diagnostic liver biopsy. Fasting blood lactate was related to liver histology and the mean was in the low normal range in the diabetics with an intact liver, whereas higher values were noted in the diabetics with a fatty liver, inflammatory changes and an increase in fibrous trabeculae. Similarly, in the diabetics with an abnormal liver, there was a tendency for pyruvate to be elevated, and body weights and serum insulin concentrations were higher than in the NIDD with an intact liver. P-450 was inversely related to liver histology and its content was reduced in association with increases in fat and fibrous tissues. P-450 was significantly correlated with lactate (rs -0.79), pyruvate (rs -0.65) and serum insulin (rs -0.53). The results revealed close associations between blood lactate, hepatic structure and microsomal enzyme activity, and emphasize that liver function is an important consideration when lactate metabolism is evaluated in NIDD.
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PMID:Blood lactate, hepatic histology and microsomal enzyme activity in non-insulin-dependent diabetics. 661 29


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