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)

Effects of chronic ethanol consumption, withdrawal and fasting on the free cytosolic NADP+/NADPH ratio and NADPH-regenerating enzyme activities of rat liver were studied. Ethanol consumption was shown to decrease the NADP+/NADPH ratio in non-fasted rats, and both ethanol withdrawal and fasting in ethanol-fed animals appeared to increase the ratio to the normal or higher level. Any treatment of rats caused the complex interaction on hepatic NADPH-regenerating enzyme activities, none of the enzyme activity correlating with the free cytosolic NADP+/NADPH ratio. Relationship between free cytosolic NADP+/NADPH ratio and lipogenic capacity of withdrawn rat liver is discussed, and a hypothesis for development of the fatty liver is suggested.
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PMID:A comparison between effects of chronic ethanol consumption, ethanol withdrawal and fasting in ethanol-fed rats on the free cytosolic NADP+/NADPH ratio and NADPH-regenerating enzyme activities in the liver. 404 9

In rats, chronic ethanol feeding was found to enhance the postprandial hyperlipemia and to increase the incorporation of dietary palmitic acid-(3)H and intravenously injected L-lysine-(14)C into serum lipoproteins. The main increases of total amount, labeling, and specific activity of lipid and protein occurred in the d < 1.019 lipoprotein fraction. Fat absorption and the clearance of injected chylomicrons were not affected by ethanol feeding. Blocking of lipoprotein and chylomicron removal with Triton did not prevent the action of ethanol on serum lipids, indicating that the ethanol effect is not likely due to defective removal of lipids from the circulation. Ethanol enhanced the incorporation of chylomicron fatty acids into newly synthetized very low density lipoproteins, as shown by an increased reappearance of the fatty acid label into the lipids of this fraction after injection of palmitate-(14)C/glycerol-(3)H doubly labeled chylomicrons. These results indicate that alcoholic hyperlipemia is due, at least in part, to an increase in newly synthetized lipoproteins. The hyperlipemia produced by ethanol was accompanied by hepatic steatosis. The simultaneous production of fatty liver and hyperlipemia makes it unlikely that defective lipoprotein synthesis or secretion is a primary mechanism for the pathogenesis of the alcoholic fatty liver.
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PMID:Efcts of chronic ethanol feeding on serum lipoprotein metabolism in the rat. 544 77

The effects on lipid metabolism of long-term feeding of large amounts of ethanol or glucose differed from those that have been reported in short-term experiments. Three groups of male rats were investigated. The first was fed lab chow and 15% (v/v) ethanol ad lib.; the second was pair-fed with the first and given isocaloric amounts of glucose in lieu of ethanol; the third was fed lab chow and water ad lib. All three groups consumed nearly the same number of calories, and about 30% of the calories in the first group were derived from ethanol. Neither glucose nor ethanol added to a nutritionally adequate diet promoted the development of a fatty liver, although both stimulated acetate-(14)C utilization for hepatic lipid synthesis. In all three groups more than 80% of the label in hepatic lipid was found in fatty acids, and the distribution of label amongst the fatty acids of different chain lengths was virtually the same. Ethanol decreased while glucose increased the quantity of lipid in fat depots, and each altered the fatty acid composition of the lipids in adipose tissue, kidney, liver, and hepatic subcellular fractions in a different manner. The most striking of these changes was the relative increase in monounsaturated fatty acids and the decrease in essential fatty acids produced by glucose.
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PMID:Effects of prolonged ingestion of glucose or ethanol on tissue lipid composition and lipid biosynthesis in rat. 594 32

1. The influence of ethanol on the metabolism of perfused livers from normal rats and rats in various stages of development of dietary cirrhosis was studied. A choline-deficient, low-protein and high-fat diet was used. Results were obtained on oxygen consumption and carbon dioxide production, on glucose release and uptake by the liver and on changes in the concentrations of lactate and pyruvate and of beta-hydroxybutyrate and acetoacetate in the perfusion medium. 2. Oxygen consumption and carbon dioxide production were lower in fatty and cirrhotic livers than in normal livers. Ethanol had no effect on the oxygen consumption of any of the various livers. After addition of ethanol to the perfusion medium carbon dioxide production ceased almost completely in normal livers. Only a slight decrease in the carbon dioxide production occurred in fatty and cirrhotic livers. 3. With every type of liver glucose was released from the liver into the perfusion medium during the initial control period. This release continued after the addition of ethanol to the perfusion medium in experiments with normal and fatty livers, whereas with cirrhotic livers a marked uptake of glucose from the medium was found. A simultaneous release of the glycolytic end products lactate and pyruvate into the medium occurred. 4. The production of ketone bodies was equal in normal and early fatty livers (6 weeks on the fat diet). It was smaller in late fatty livers (3-4 months on the fatty diet) and in cirrhotic livers. 5. The lactate/pyruvate concentration ratio in the perfusion medium increased from 11 to 67 with normal livers, from 12 to 16 with early fatty livers, from 13 to 26 with late fatty livers and from 21 to 55 with cirrhotic livers when the livers were perfused with a medium containing ethanol. The beta-hydroxybutyrate/acetoacetate concentration ratio increased from 1.2 to 8.4 in normal livers, from 2.0 to 2.8 in early fatty livers, from 1.2 to 2.4 in late fatty livers and from 2.1 to 4.0 in cirrhotic livers when ethanol was added to the medium. 6. The effects of ethanol on liver metabolism during the development of dietary cirrhosis are discussed and related to human fatty liver and cirrhosis during chronic ethanol consumption.
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PMID:Influence of ethanol on the metabolism of perfused normal, fatty and cirrhotic rat livers. 596 89

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

Ethanol-associated fatty liver was induced in rats fed a nutritionally deficient liquid diet containing 36% of total calories as ethanol. Control rats received the same diet with sucrose substituted isocalorically for ethanol. After 40 days, hepatic lipid content of the ethanol-maintained animals was four-fold greater than controls and ultrastructural changes in hepatocytes were well established. Clearance of intravenously administered human enterokinase from the circulation as well as bile flow were, however, the same in both groups. The proportion of enterokinase appearing in catalytically active form in bile after intravenous injection was substantially greater in the ethanol-maintained animals than the isocaloric controls; the difference was highly significant (p less than 0.001) and reached two- to four-fold after 70 days on the diet. These findings would suggest that the ability of hepatocytes to degrade enterokinase cleared from the blood may be bypassed or impaired by prolonged ethanol consumption and a deficient diet. Catalytically active enterokinase in bile may participate in the development of some types of acute necrotising pancreatitis.
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PMID:Biliary excretion of enterokinase in rats: studies in alcoholic rats with fatty liver. 633 13

The lipid-lowering effect of carnitine and its precursors, namely lysine plus methionine, was examined in male Sprague-Dawley rats fed ethanol as 36% of the total calories. Ethanol caused typical hepatic steatosis characterized by significant accumulation of total lipids, triglycerides, cholesterols, phospholipids, and free fatty acids. Supplementation of the ethanol diet with 1% DL-carnitine, 0.5% L-lysine, and 0.2% L-methionine significantly lowered ethanol-induced increases of various lipid fractions, with the exception of free fatty acids. The lipid-lowering effect of carnitine was superior to that of its precursors and their effect together was no greater than that of carnitine alone. The triglyceride contents of liver and plasma were related inversely to the levels of carnitine and acyl carnitines. It is concluded that dietary carnitine more effectively than its precursors prevented alcohol-induced hyperlipemia and accumulation of fat in livers. Thus, a deficiency of functional carnitine may indeed exist in chronic alcoholic cases.
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PMID:Ameliorating effects of carnitine and its precursors on alcohol-induced fatty liver. 642 29

Male Wistar rats were maintained for 30 days on an independent and continuous intragastric infusion of ethanol and nutritionally defined liquid diet containing only a small amount of corn oil (CO-4.9% calories). Ethanol intake was progressively increased from 32% to 40.4% of the total calories to maintain a high degree of intoxication during this period. Rats in the control group were infused with an isocaloric diet in which alcohol was replaced by dextrose. The liver triglyceride (TG) content of rats given alcohol (61.5 +/- 16.4 mg/g) was ca. 10-fold greater than that of controls (5.9 +/- 2.1 mg/g) and similar to that observed previously in rats fed an ethanol diet containing high levels of fat (35% and 43% calories). In TG of fatty liver, the level of 18:2 was small (3%), even though CO in the diet contained a high level of this acid. Furthermore, 16:1 and 16:0 contents were markedly elevated (16% and 40%, respectively) despite the fact that CO did not contain 16:1 and had only a small amount of 16:0. Liver TG having a fatty acid (FA) composition markedly different from that of CO and the presence of high levels of 16:1 and 16:0 indicate that the TG accumulated in the fatty liver originated from hepatic lipogenesis rather than from dietary fat.
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PMID:Hepatic origin of triglycerides in fatty livers produced by the continuous intragastric infusion of an ethanol diet. 673 18

Ethanol was found to be capable to stimulate the microsomal xenobiotic-metabolizing enzyme system of human liver. However, this effect was seen only in cases of alcoholic liver damage (fatty liver, alcoholic hepatitis). Alcoholics without alcoholic liver injury had enzyme activities comparable to control patients, who had no liver disease. On ethanol abstinence the enzyme stimulation was reversible within 20 days. Stimulation of xenobiotic-metabolizing enzyme activity in alcoholic liver disease seems to be related to ethanol induced toxicity. The highest enzyme activities were observed in patients on enzyme inducing drugs (2- to 6 fold increase), whereas in alcoholic liver disease enzyme activities were doubled. These results suggest that the stimulation of the microsomal enzyme system caused by ethanol is different from the enzyme induction seen on inducing drugs.
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PMID:[Foreign substance-degrading enzyme system of the human liver. Modification by alcohol, other exogenous factors and liver diseases]. 679 Mar 94

Development of alcohol-related liver and other diseases appears to be modified by host and environmental factors that include diet and nutritional status, exposure to other drugs and toxins, and infection. The relative importance of alcohol toxicity and malnutrition in the induction of fatty liver and cirrhosis, the subject of this report, has been debated. Male rhesus (M mulatta) monkeys were fed purified liquid diets, adequate or marginally deficient in lipotropes (choline, methionine, and folate), containing ethanol to supply 40-50% of calories for 1.5-4.5 years. Controls, fed the diets with sucrose and fat isocalorically substituted for ethanol, grew well and were clinically normal. Ethanol-fed monkeys in both diet groups failed to gain weight and were slightly anemic, with mild derangements of serum electrolytes and small amounts of fat in their livers. None had fibrosis or cirrhosis until the severity of the lipotrope-deficiency was increased; then two of four deficient animals developed cirrhosis and one developed fibrosis. (The severe deficiency induced weight loss and fatty liver, but not fibrosis, in one of two controls.) We conclude that alcohol does not induce hepatic fibrosis or cirrhosis in rhesus monkeys fed a nutritionally complete diet, a result supported by studies in rats and another monkey, M radiata. Alcohol does induce cirrhosis when fed in combination with a lipotrope-deficient diet that is not, by itself, cirrhogenic.
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PMID:Ethanol and diet interactions in male rhesus monkeys. 692 13


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