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)

The labeled bile salt tolerance test is the measure of the decrease in plasmatic radioactivity after intravenous injection of carboxyl-14C-labeled chenic acid. The label is distributed in the blood, taken up by hepatocytes and then secreted in the bile. The decrease in plasmatic radioactivity during the 4 h following the injection follows a bi-exponential curve. It has been studied in 6 normal subjects, 4 patients equipped with "T tube", 3 cases of acute viral hepatitis, 4 cases of hepatic steatosis, and 6 cases of hepatic cirrhosis. The first slope (b1) represents the hepatic uptake of the label. It is lowered in cases of viral hepatitis and in cirrhosis. The second slope (b2) represents hepato-biliary secretion of the label. It is lowered in patients equipped with a "T tube". From 100 min after the injection, the plasma concentration of radioactivity remains constant. This is the residual value (R), and it is very low in normal subjects. It is increased in cases of acute viral hepatitis and cirrhosis, indicating displacement of a fraction of the bile salt pool into peripheral blood. After a standard meal, the R value is not modified in the normal subject. In cases of steatosis and cirrhosis, a temporary peak may be seen, indicating recirculation of the label towards the periphery due to a porto-systemic shunt or a hepatocyte lesion.
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PMID:[Clinical application of the radiolabeled bile salt tolerance test]. 67 9

Fatty infiltration of liver and formation of cholesterol stones are significant problems following jejunoileal bypass for morbid obesity. This report evaluates hepatic lipid metabolism and fat absorption in genetically obese, bypassed, and lean Zucker rats. Ninety percent jejunoileal bypass was performed in 12 (500 grams) obese rats (BP). Similar numbers of unoperated "fat rats" (FR) and lean litter mates (LR) were controls. Food consumption, weight gain or loss, and fecal fat were evaluated. At 4 weeks serum triglycerides, hepatic cholesterol, total lipids, triglycerides, and hepatic synthesis of fatty acids and cholesterol were measured in vivo. Food intake was excessive in FR's (23.8 +/- 0.7 gm/day), decreased in BP (18.3 +/- 2.3 gm/day), and lowest in LRss ( less than 0.05) and excessive fecal fat excretion (p less than 0.05). Serum triglycerides were elevated in FR's (284 +/- 32 mg/dl), reduced in BP rats (148 +/- 20 mg/dl) (p less than 0.05), and low in LR's (86 +/- 16 mg/dl). Total hepatic lipids, triglycerides, and hepatic synthesis of fatty acids were elevated in FR's (p less than 0.05) and were unchanged by bypass. Hepatic cholesterol was similar in all groups. Hepatic synthesis of cholesterol, however, was increased significantly in bypassed rats (p less than 0.05), (BP--102 +/- 22 micronnmole/"C2"/minute/gm, FR--39 +/- 6.0, LR--30 +/- 4.0). Jejunolileal bypass in FR's results in weight loss, decreased food intake, increased fecal fat, decreased serum triglycerides, and increased hepatic synthesis of cholesterol. Bypass had little effect on reducing elevated hepatic lipids, triglycerides, or fatty acid synthesis in FR's. These data suggest that following bypass increased hepatic cholesterol synthesis (as a precursor for bile acids) is related to interruption of the enterohepatic circulation and bile salt pool depletion. This implies that excess synthesis of hepatic cholesterol results in supersaturation of bile which is choletithocenic and may explein in part the increased incidence of gall stones observed following jejunoileal bypass.
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PMID:Increased hepatic synthesis of cholesterol following jejunoileal bypass. 87 Oct 14

Percutaneous liver biopsies obtained from patients with a history of chronic alcoholism and normal liver, fatty liver, alcoholic hepatitis, or active cirrhosis were incubated with tritiated proline to determine the pattern of collagen biosynthesis in these conditions. Incorporation of labeled proline and hydroxyproline into salt-soluble and insoluble fractions of collagen was evaluated by radiochemical analysis and tissue localization documented by autoradiography. Biopsy specimens of alcoholic hepatitis and cirrhosis exhibit a significant increase in the amount of radioactive proline and hydroxyproline in salt-soluble and insoluble collagen. Marked accumulation of radioactivity occurred over bile ducts, fibroblasts, and collagen fibers in the portal area and over hepatocytes, fibroblasts, and collagen fibers in the centrilobular area. Fatty liver is associated with an increase in uptake of proline and hydroxyproline in the salt-soluble fraction of collagem; silver grains appear in the periphery of fat-laden cells and in areas of focal inflammation. Digestion by collagenase indicates that labeling over fibroblasts and collagen reflects active synthesis, whereas, entry of proline into the cell protein pool is responsible for accumulation of radioactivity in other sites. In vitro ethanol causes a significant increase in the incorporation of proline and hydroxyproline into collagen in biopsy specimens of alcoholic hepatitis or active cirrhosis, but has no effect on collagen synthesis by normal or fatty liver.
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PMID:Collagen biosynthesis in liver disease of the alcoholic. 117 Feb 67

Evidence of hepatic dysfunction (clinically, chemically, and morphologically) and biliary-tract abnormalities is common in patients receiving TPN. The entity might present as hepatocellular injury (fatty liver, steatonecrosis), intrahepatic cholestasis, acalculous cholecystitis, or cholelithiasis. Infants manifest primarily intrahepatic cholestasis, whereas adults manifest fatty liver early and intrahepatic cholestasis later in the course of therapy. Both groups are at risk for the development of biliary-tract abnormalities. Although most of these changes in the adult are mild and reversible, a small number of patients have recently been reported to develop progressive liver disease. In infants, however, the changes may be more severe, and lead more frequently to progressive liver disease and death. Although this progression to chronic liver disease is worrisome, it is uncertain whether, in patients on long-term therapy, it is due to the TPN or to other conditions or therapies associated with their clinical condition. The pathogenesis of each of these lesions may be multifactorial, including carbohydrate overfeeding, essential-fatty-acid deficiency, amino-acid deficiencies or imbalances, carnitine deficiency, bile-salt toxicity, lipid emulsions, bile-flow reduction, and gallbladder stasis. Therapies in these patients are aimed at alterations in the preceding etiologies (decreased glucose loads, contraction of the gallbladder). Further work is necessary to delineate the exact mechanisms of this entity, especially with regard to the causal relationships of TPN and this entity and to the development of chronic liver disease.
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PMID:Hepatobiliary abnormalities associated with total parenteral nutrition. 250 58

Lipid peroxidation has been induced by means of an atherogenic diet causing hypercholesterolaemia, hypertriglyceridaemia, increased LDL and decreased HDL serum fractions in addition to the fatty degeneration, vacuolization of the liver cells and accumulation of malondialdehyde in the liver. Increased release of acid phosphatase and N-beta-glucuronidase was also observed pointing to cholesterol-induced lysosomal membrane damage. In response to pretreatment with, and simultaneous administration of, 6,6'-methylene bis (2,2-dimethyl-4-methane sulphonic acid sodium salt-1,2-dihydroquinoline) the signs and symptoms of fatty liver degeneration, the tissue, plasma and platelet malondialdehyde concentrations and the LDL serum fraction significantly decreased and HDL serum fraction increased. Lisosomal membrane stability was restored, resulting in physiological acid phosphatase and N-beta-glucuronidase activities. The pathological and clinical aspects of lipid peroxidation in several diseases of the digestive organs and the suggested therapeutic uses of non-toxic radical scavengers have been outlined.
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PMID:Liver lipid peroxidation induced by cholesterol and its treatment with a dihydroquinoline type free radical scavenger in rabbits. 653 29

Hypernatremic states, often the result of hypothalamic osmoreceptor dysfunction in humans, are sometimes accompanied by hyperlipemia. To investigate whether hypernatremia could cause hyperlipemia we induced hypernatremia in three groups of rats with their respective controls: Group A rats received hypertonic saline alone intragastrically; group B animals were pair-fed and tap water was substituted for hypertonic saline in the treated group; in group C the rats were again fed intragastrically with a liquid diet mixed with hypertonic saline. Rats receiving excess salt had mean serum Na+ concentrations exceeding 159 mmoles/l. While the serum triglyceride values were significantly higher in all hypernatremic rats, hepatic triglyceride content was greater only in group C rats (p less than .01). Serum free fatty acids and ketone bodies were also higher in group C rats (p less than .01) as compared to controls. These data suggest that hypernatremia by itself leads to hyperlipemia and a fatty liver.
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PMID:Hypernatremia induces hyperlipemia and a fatty liver. 684 93

Chronic administration of a soybean-derived polyenylphosphatidylcholine (PPC) extract prevents the development of cirrhosis in alcohol-fed baboons. To assess whether this phospholipid also affects earlier changes induced by alcohol consumption (such as fatty liver and hyperlipemia), 28 male rat littermates were pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 21 d, and killed 90 min after intragastric administration of the corresponding diets. Half of the rats were given PPC (3 g/l), whereas the other half received the same amount of linoleate (as safflower oil) and choline (as bitartrate salt). PPC did not affect diet or alcohol consumption [15.4 +/- 0.5 G/(kg.d)], but the ethanol-induced hepatomegaly and the hepatic accumulation of lipids (principally triglycerides and cholesterol esters) and proteins were about half those in rats not given PPC. The ethanol-induced postprandial hyperlipemia was lower with PPC than without, despite an enhanced fat absorption and no difference in the level of plasma free fatty acids. The attenuation of fatty liver and hyperlipemia was associated with correction of the ethanol-induced inhibition of mitochondrial oxidation of palmitoyl-1-carnitine and the depression of cytochrome oxidase activity, as well as the increases in activity of serum glutamate dehydrogenase and aminotransferases. Thus, PPC attenuates early manifestations of alcohol toxicity, at least in part, by improving mitochondrial injury. These beneficial effects of PPC at the initial stages of alcoholic liver injury may prevent or delay the progression to more advanced forms of alcoholic liver disease.
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PMID:Polyenylphosphatidylcholine attenuates alcohol-induced fatty liver and hyperlipemia in rats. 927 63

The purpose of this work was to examine whether ursodeoxycholate (UDC), a hydrophilic bile salt, could reduce mitochondrial liver injury from chronic ethanol consumption in rats. Animals were pair-fed liquid diets containing 36% of calories as ethanol or isocaloric carbohydrates. They were randomly assigned into 4 groups of 7 rats each and received a specific treatment for 5 weeks: control diet, ethanol diet, control diet + UDC, and ethanol diet + UDC. Respiratory rates of isolated liver mitochondria were measured using a Clark oxygen electrode with sodium succinate as substrate. Mitochondria from rats chronically fed ethanol demonstrated an impaired ability to produce energy. At the fatty liver stage, the ADP-stimulated respiration (V3) was depressed by 33%, the respiratory control ratio (RC) by 25% and the P/O ratio by 15%. In ethanol-fed rats supplemented with UDC, both the rate and efficiency of ATP synthesis via the oxidative phosphorylation were improved: V3 was increased by 35%, P/O by 8%. All the respiratory parameters were similar in control group and control + UDC group. On the other hand, the number and size of mitochondria were assessed by electron microscopy and computer-assisted quantitative analysis. The number of mitochondria from ethanol-treated rats was decreased by 29%, and they were enlarged by 74%. Both parameters were normalized to control values by UDC treatment. These studies demonstrate that UDC has a protective effect against ethanol-induced mitochondrial injury by improving ATP synthesis and preserving liver mitochondrial morphology. These UDC positive effects may contribute to the observed decrease in fat accumulation and may delay the progression of alcoholic injury to more advanced stages.
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PMID:Ursodeoxycholate protects against ethanol-induced liver mitochondrial injury. 987 Jul 12

Abcb11 encodes for the liver bile salt export pump, which is rate-limiting for hepatobiliary bile salt secretion. We employed transthyretin-Abcb11 and BAC-Abcb11 transgenes to develop mice overexpressing the bile salt export pump in the liver. The mice manifest increases in bile flow and biliary secretion of bile salts, phosphatidylcholine, and cholesterol. Hepatic gene expression of cholesterol 7alpha-hydroxylase and ileal expression of the apical sodium bile salt transporter are markedly reduced, whereas gene expression of targets of the nuclear bile salt receptor FXR (ileal lipid-binding protein, short heterodimer partner (SHP) is increased. Because these changes in gene expression are associated with an increased overall hydrophobicity of the bile salt pool and a 4-fold increase of the FXR ligand taurodeoxycholate, they reflect bile salt-mediated regulation of FXR and SHP target genes. Despite the increased biliary secretion of bile salts, fecal bile salt excretion is unchanged, suggestive of an enhanced enterohepatic cycling of bile salts. Abcb11 transgenic mice fed a lithogenic (high cholesterol/fat/cholic acid) diet display markedly reduced hepatic steatosis compared with wild-type controls. We conclude that mice overexpressing Abcb11 display an increase in biliary bile salt secretion and taurodeoxycholate content, which is associated with FXR/SHP-mediated changes in hepatic and ileal gene expression. Because these mice are resistant to hepatic lipid accumulation, regulation of Abcb11 may be important for the pathogenesis and treatment of steatohepatitis.
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PMID:Hepatic overexpression of murine Abcb11 increases hepatobiliary lipid secretion and reduces hepatic steatosis. 1457 Sep 29

The case of a French child, born of consanguineous parents of Tunisian origin, is described. He showed a severe multisystem disease with dyserythropoietic, sideroblastic anaemia, delayed neurological development with hypotonia and convulsions, salt-losing nephropathy, chronic watery diarrhoea, lactic acidosis with mitochondrial dysfunction, brittle hair, hypergammaglobulinaemia, fatty liver with intermittent transaminasaemia, and terminal pulmonary fibrosis. Two siblings, of both sexes, were stillborn; two more lived only a short time. One sister is alive and well. SDS gel analysis of the red cell membranes showed a deficiency within 'Band 7' at 32 kDa. Analysis of the gene encoding 'stomatin', or 'erythrocyte membrane protein 7.2b', the principal protein of 'Band 7', revealed a complex series of aberrant spliceforms centred around exon 3, for which no explanatory genomic lesion could be found. The true underlying molecular cause of this condition remains obscure, but it suggests that the stomatin gene should be studied in other cases.
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PMID:A family showing recessively inherited multisystem pathology with aberrant splicing of the erythrocyte Band 7.2b ('stomatin') gene. 1497 Jul 44


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