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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute effects of the PCB (polychlorinated biphenyls) mixture (Aroclor 1254) on microsomal enzymes and on synthesis and turnover of microsomal and cytoplasmic lipids of rat liver were investigated. Six daily i.p. injections of 25 and 50 mg PCB/kg body weight resulted in increased liver weight and liver to body weight ratios. When compared to controls PCB treatment resulted in a six-fold increase in amount of cytochrome P-450. Activities of NADPH-cytochrome c reductase, ethylmorphine demethylase and inosine diphosphatase were increased whereas glucose-6-phosphatase values were decreased by PCB exposure. Analysis of liver homogenate and microsomal fraction revealed an increase in lipid in PCB-exposed animals. Phospholipids, cholesterol and triglyceride were significantly increased after PCB exposure; however, the greatest percentage increase was seen in the triglyceride pool. The finding of an increase in microsomal triglyceride to phospholipid ratios with exposure to PCB is suggestive of an increase in membrane-enclosed lipid (liposomes). Studies with labelled glycerol indicated that the PCB-induced fatty liver resulted from increased half life but not increased synthesis of liver lipid moieties. The rate of incorporation of leucine into microsomal membrane and albumin was somewhat enhanced in rats exposed to PCB indicative of increased protein synthesis. Morphological studies showed increased occurrence of lipid material, both in cytoplasmic droplets and within rough and smooth-surfaced endoplasmic reticulum. Proliferation of smooth endoplasmic reticulum and flattened Golgi cisternae with no secretion granules containing lipoprotein particles characterized the liver from animals exposed for 6 days. The increase in lipid within membranes of the endoplasmic reticulum together with the flattened Golgi lacking typical secretory vesicles indicates a defect in transport of lipoproteins from the endoplasmic reticulum to the Golgi apparatus and may be the cause of the PCB-induced fatty liver.
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PMID:Studies on the cellular toxicity of polychlorinated biphenyls (PCBs). I. Effect of PCBs on microsomal enzymes and on synthesis and turnover of microsomal and cytoplasmic lipids of rat liver- a morphological and biochemical study. 9 1

The mechanism of liver enlargement and anti-fatty liver effect of NKK-105 in the rat were investigated by the mesurement of drug-metabolizing enzyme activities and morphological changes in liver tissue detected using electron microscopy. A single administration of NKK-105(250, 500, 1000 mg/kg, p.o.) induced an apparent increase in liver weight. The elevation of aminopyrine demethylase activity and slight increase in microsomal cytochrome b5 and cytochrome P-450 content were seen with the administration of NKK-105. NKK-105 inhibited lipid peroxide formation in mitochondrial and microsomal fractions. Total lipid content of liver decreased at 12 hr after the administration of NKK-105. Lipid peroxide formation in mitochondrial and microsomal fractions was markedly inhibited by the addition of NKK-105 (1 X 10(-3)M), in vitro. Disarrangement of rough endoplasmic reticulum and increase in smooth endoplasmic reticulum were observed by the administration of NKK-105. The decrease in drug-metabolizing enzymes caused by CCl4 or ethionine was protected in the combination with NKK-105. NKK-105 markedly inhibited the elevation of lipid peroxide formation caused by CCl4 or ethionine. Similar effects on lipid peroxide formation were also obtained in vitro. These results suggest that the enlargement induced by NKK-105 indicates a functional not a toxic response. The inhibition of lipid peroxide formation in mitochondrial and microsomal fractions may thus play an important role in the mechanism of anti-fatty liver effect of NKK-105 on the CCl4 or ethionine-induced fatty liver.
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PMID:[Effects of diispropyl 1, 3-dithiol-2-ylidene malonate (NKK-105) on the drug-metabolizing enzymes and fine structure of rat liver (author's transl)]. 12 Feb 99

The sequential pattern of lipid accumulation and associated biochemical changes were studied in two commonly used experimental models of nutritional fatty liver in rats. Female rats were maintained for 8 weeks on high fat, low protein diets containing adequate methionine and choline, and drinking water ad libitum (Diet 1), or deficient in methionine and choline and containing 20% ethanol as a substitute for drinking water (Diet 2). Histologically, there was a progressive increase in liver lipids, mainly in the periportal areas. Occasional foci of liver cell necrosis with lipogranuloma formation occurred in areas of severe fatty change. These changes appeared earlier and were more marked in rats maintained on Diet 2. Electron micrographs revealed large lipid droplets in the liver cells, which sometimes contained myelin figures. The mitochondria were enlarged, distorted and appeared as amorphous structures with disorientated cristae in rats on Diet 1, whereas they had a condensed conformation in rats maintained on Diet 2. Rough endoplasmic reticulum was fragmented and degranulated particularly in rats on Diet 1, and smooth endoplasmic reticulum showed hyperplasia and vesiculation in rats on Diet 2. There was a progressive increase in the total liver lipids and triglycerides in both the groups of rats. This fatty change was accompanied by a significant increase in hepatic 3-hydroxybutyrate, acetoacetate, malate, 2-oxoglutarate, citrate, lactate, ammonia, glutamate, alanine and aspartate, and a significant decrease in oxaloacetate, urea and glucose concentrations. The mass action ratios for alanine aminotransferase, aspartate amino transferase, and glutamate dehydrogenase, generally moved in a parallel direction. Hepatic ATP content was considerably reduced accompanied by a decrease in [ATP]/[ADP] ratios and a significant increased in [lactate]/[pyruvate] and [3-hydroxybutyrate]/[acetoacetate] ratios. There was a corresponding decrease in the [NAD+]/[NADH] ratios both in the cytoplasmic and mitochondrial compartments. These biochemical changes were particularly severe in rats maintained on Diet 1 and Diet 2 for 8 weeks. There was a very good relationship between impaired mitochondrial and endoplasmic reticulum functions, redox and phosphorylation states, and the relevance of their changes to the fate of fatty liver cells.
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PMID:Lipid accumulation in the rat liver: a histological and biochemical study. 23

1. The effect of ethanol on the metabolism of [1-(14)C]palmitate in rat liver was investigated in a single-pass perfusion system at concentrations of 10mm- or 80mm-ethanol and 0.2mm- or 1mm-palmitate. 2. After the perfusion the hepatic lipid was isolated in subcellular fractions. The two major fractions contained triacylglycerol from cytoplasmic lipid droplets and from endoplasmic reticulum plus Golgi apparatus respectively. 3. In experiments with 0.2mm-palmitate perfusion with 10mm- or 80mm-ethanol did not measurably increase the esterification, and the oxidation was markedly decreased and the fatty acid uptake was not affected. 4. Perfusion with ethanol, at 1mm-palmitate, increased the fatty acid uptake, increased esterification and decreased oxidation. The effects of 10mm- and 80mm-ethanol were similar. The incorporation of [1-(14)C]palmitate into triacylglycerol in cytoplasmic lipid droplets was not affected statistically significantly by ethanol. Ethanol increased the incorporation of [1-(14)C]palmitate into di- and tri-acylglycerol in the membranous fraction. Estimated chemically, the contents of di- and tri-acylglycerol were only slightly affected by ethanol. These results suggest that the effect of ethanol was to increase the turnover of fatty acids in triacylglycerol rather than to increase its accumulation. 5. The results indicate that an increased concentration of fatty acids is more important for the formation of acute fatty liver in fed rats than are the direct effects of ethanol on hepatic fatty acid metabolism.
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PMID:Metabolism of palmitate in perfused rat liver. Effect of low and high ethanol concentrations at various concentrations of palmitate in the perfusion medium. 53 22

1. Rats were treated for 4 weeks with liquid diets that contained, on the basis of energy content, 35% fat, 18% protein and 47% carbohydrate (high-fat diet) or 35% fat, 18% protein, 11% carbohydrate and 36% ethanol (high-fat/ethanol diet). 2. The livers were perfused with 1mm-[1-(14)C]palmitate and with 0, 10mm- or 80mm-ethanol. The oxidation and esterification of palmitate was measured. Two subcellular pools of triacylglycerol were separated; one contained triacylglycerol from cytoplasmic lipid droplets and the other contained triacylglycerol from the endoplasmic reticulum and Golgi apparatus. 3. In the presence of ethanol, liver from rats fed on the high-fat diet esterified about 70% of the [1-(14)C]palmitate taken up compared with 90% in liver from rats fed chow (containing 11% fat on the basis of energy content). Compared with chow diet the high-fat diet did not potentiate the effect of ethanol on storage of [1-(14)C]palmitate in hepatic triacylglycerol. The relation between the fat content of the diet and the degree of fatty liver induced by by ethanol [Lieber & DeCarli (1970) Am. J. Clin. Nutr.23, 474-478] is discussed. 4. The ethanol-containing diet increased the hepatic content of triacylglycerol 4-fold and the increase was exclusively found in the fraction suggested to contain lipid from cytoplasmic lipid droplets. The ethanol-induced fatty liver, perfused with ethanol, esterified and oxidized palmitate at rates that were quite similar to the rates found in high-fat control livers perfused without ethanol. This suggests that the fatty liver had adapted to the presence of ethanol with respect to palmitate metabolism. 5. O(2) and ethanol uptake by the livers were not affected by the ethanol-containing diet.
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PMID:Metabolism of palmitate in perfused rat liver. Effect of ethanol in livers from rats fed on a high-fat diet with or without ethanol. 53 23

The addition of 1 per cent orotic acid to a sucrose-enriched semipurified diet results in markedly fatty liver when fed to rats for 7 to 22 days. Light microscopy reveals lipid droplets, mostly small, distributed throughout the cytoplasm of all hepatocytes. Electron microscopy shows that all the endoplasmic reticulum (ER) is broken into vesicles. Within the interior (cisterna) of each vesicle one or more lipid droplets are present. Morphologic signs of normal lipid transport (ER to Golgi apparatus to space of Disse) disappear: the Golgi elements are flattened and lack very low density lipoproteins particles; the Golgi-derived secretory vacuoles are not present. Biochemical analyses show an increase in hepatic triacylglycerol levels, to approximately 8 times the levels of sucrose-fed controls by the 7th day, 18 times by the 15th day, and 25 times by the 22nd day. Hepatic cholesterol levels increase, 2- to 4-fold. Serum triacylglycerol levels fall markedly; serum cholesterol levels are reduced. Immunoelectrophoretic determinations show that the apoprotein B component of plasma lipoproteins is practically absent at 7 days and increases slightly at 22 days. Reversal of an orotic acid-induced fatty liver is achieved by adding ethyl chlorophenoxyisobutyrate (clofibrate or CPIB) to the diet. By 8 to 16 days the ER of the hepatocytes returns to its usual parallel configuration and lipid droplets are not seen within its cisternae. Morphologic features of normal lipid transport reappear. GERL becomes prominent, distended with small particles, interpreted as lipid undergoing degradation. Lipid-containing residual bodies are common. Peroxisomes are more numerous than in hepatocytes of control rats. Liver triacylglycerol levels approach sucrose-fed control levels, and serum triacylglycerol levels return to chow-fed control levels. Hepatic cholesterol levels are similar to those of sucrose-fed and chow-fed controls, whereas serum cholesterol levels are lower. Serum apoprotein B levels return to chow-fed control levels. A sequence of events terminating in the removal of lipid from the hepatocytes is suggested by observation of morphologic changes following chlorophenoxyisobutyrate administration. This appears to involve transport of lipid into the cytosol where it accumulates as large spheres. Extensive accumulations of smooth ER appear. The cytosol lipid then disappears as the rough ER develops. Peroxisomes and mitochondria are prominent during the reversal process.
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PMID:Reversal of orotic acid-induced fatty liver in rats by clofibrate. 83 35

Absorption of 57Co-labelled vitamin B12 - intrinsic factor (IF) complex and its binding to mucosal precipitate and brush border fractions of rat small intestine was studied in rats pair-fed with a liquid diet containing ethanol 5 g/100 ml, 35% of calories, or isocalorically substituted sucrose. IF was obtained from rats fasted for 18 h. and for each experiment the amount of vitamin B12 added was the minimum required to achieve maximum binding to IF. Rats fed alcohol exhibited hepatic steatosis, proliferation of smooth endoplasmic reticulum, and disordered mitochondria after 6 weeks on the diet, and absorption of vitamin B12, fed with IF by stomach tube, was reduced signficantly. In contrast, binding of 57Co-labelled vitamin B12 -IF complex to mucosal precipitate and brush border fractions was never less than that of fractions from control rats at 4, 8 and 12 weeks on the alcohol diet. Furthermore, binding to the brush border was significantly greater in alcohol-fed rats at 12 weeks whether expressed per unit of beta-naphthylamidase (EC 3.4.1.1) activity or per milligram of protein. Total mucosal sucrase (EC 5.2.1.26) and beta-naphthylamidase were unchanged or slightly increased (beta-naphthylamidase at 12 weeks) on the alcohol-containing diet indicating that total brush border membrane was not reduced. Total brush border binding activity was the same in alcohol-fed and control rats at each time period. These results indicate that malabsorption of vitamin B12 in rats fed alcohol cannot be due to decreased binding of the vitamin B12 - IF complex by brush border membrane receptors, or secondary to a net decrease in membrane receptors.
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PMID:Lack of effect of alcohol on small intestinal binding of the vitamin B12 - intrinsic factor complex. 97 75

This study reproduces in experimental animals the sequential development of all the liver lesions seen in the human alcoholic: in 15 baboons fed ethanol, all developed fatty liver, five progressed to hepatitis, and five had cirrhosis. Maintenance of a nutritionally adequate regimen despite the intake of inebriating amounts of ethanol (50% of total calories) was achieved by incorporation of the ethanol in a totally liquid diet. Upon ethanol withdrawal, signs of physical dependence, such as seizures and tremors, developed. Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis) and differed from the alterations produced by choline and protein defiencies. At the fatty liver stage, some "adaptive" increases in activity of microsomal enzymes [aniline hydroxylase (EC 1.14.14.1) and the microsomal ethanol oxidizing system] were observed, but these tended to disappear with the development of hepatitis and cirrhosis. Fat accumulation was also much more pronounced in the animals with the hepatitis as compared with those with simple fatty liver (an 18-fold compared with 3- to 4-fold increase in liver triglycerides). The demonstration that these lesions can develop despite an adequate diet indicates that in addition to correction of the nutritional status, control of alcohol intake is mandatory for the management of patients with alcoholic liver injury.
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PMID:Sequential production of fatty liver, hepatitis, and cirrhosis in sub-human primates fed ethanol with adequate diets. 105 27

The administration of single or multiple oral doses of hexachlorophane to yearling sheep resulted in a periportal fatty liver. The accumulation of fat is accompanied by ultrastructural changes in the hepatocyte organelles, particularly the endoplasmic reticulum and Golgi apparatus, and by decreased serum lipid and triglyceride levels. It is suggested that an impairment in the triglyceride secretory mechanism of the liver cell may be the patho-physiological basis for fatty liver. However, the changes in the liver were not accompanied by an evidence of significant impairment of liver cell function.
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PMID:An ultrastructural and biochemical study of hexachlorophane-induced fatty liver in sheep. 115 14

Malnutrition is common among alcoholics because alcohol displaces protein-, vitamin-, and mineral-containing foods in the diet, and chronic alcohol consumption results in maldigestion and malabsorption of essential nutrients. In addition, alcohol exerts direct toxic effects on both the liver and gut, resulting in structural alterations in the intestine and the development of fatty liver, alcoholic hepatitis, and cirrhosis. Liver injury is preceded by an adaptive phase characterized by accelerated metabolism of drugs (including ethanol), and hyperlipemia, secondary to hypertrophy and hyperactivity of the smooth endoplasmic reticulum. Side effects include enhanced hepatotoxicity of CCI4 and possibly energy wastage. Alcoholics should not be led to beleive that correction or prevention of nutritional deficiency will prevent liver damage in the face of continued alcohol abuse.
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PMID:Alcohol and malnutrition in the pathogenesis of liver disease.. 117 54


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