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)

Circulating hormone and metabolite profiles have been studied in ten patients with alcoholic cirrhosis, five patients with alcoholic hepatitis and/or fatty liver, and nine normal controls over a 12-h period of meals and activity. Blood glucose was elevated throughout the day in both cirrhotic and non-cirrhotic alcoholics (mean 12-h glucose; controls 5.38 +/- 0.16 (SEM) mmol/l; cirrhotics 6.98 +/- 0.30 mmol/l, P less than 0.001; non-cirrhotics 7.18 +/- 0.26 mmol/l, P less than 0.001). Non-cirrhotic alcoholics had an exaggerated insulin response to meals, whereas cirrhotic patients had hyperinsulinaemia throughout the day (mean 12-h insulin; controls 16.3 +/- 2.3 mU/l; cirrhotics 35.8 +/- 6.6 mU/l, P less than 0.02). Growth hormone levels were elevated only in patients with cirrhosis (mean 12-h growth hormone, 7.06 +/- 1.35 v. 0.85 +/- 0.17 micrograms/l, P less than 0.001). Serum cortisol was persistently elevated in cirrhotics but only in the evening in non-cirrhotic alcoholics. Lactate and pyruvate responses to meals were exaggerated in non-cirrhotic patients whereas in cirrhotics, levels were persistently raised. Blood glycerol was elevated in all alcoholic patients whereas ketone body levels were normal. Hypertriglyceridaemia was observed only in non-cirrhotic patients. No relationship between the endocrine and metabolic state was observed in either cirrhotic or non-cirrhotic patients.
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PMID:Hormone and metabolite profiles in alcoholic liver disease. 641 54

Earlier studies showed that the fatty liver, caused by feeding rats the Lieber-DeCarli alcohol diet for four weeks, was prevented if the diet was supplemented with dihydroxyacetone (22 g/l), pyruvate (22 g/l) and riboflavin (2.2 g/l). In the present study, we observed that fatty liver was prevented if the alcohol diet was supplemented with glycerol and lactate (22 g/l each) and riboflavin (2.2 g/l). Hence, the prevention of alcoholic fatty liver by the dietary supplementation with dihydroxyacetone and pyruvate may not be related to their capacity to serve as hydrogen acceptors and to oxidize NADH produced during ethanol metabolism. When rats were fed the alcohol diet supplemented with either glycerol or pyruvate, the hepatic triglyceride (TG) levels were similar to those in rats pair-fed a Lieber-DeCarli control diet in which alcohol was replaced with an isocaloric amount of dextrins. Therefore, the prevention of fatty liver does not require the simultaneous presence of several supplements. Dietary dihydroxyacetone or riboflavin did not reduce alcoholic fatty liver. Supplementation of the ethanol diet with isocaloric amounts of lactate or glucose, instead of pyruvate, did not abolish the development of fatty liver but caused a marked reduction in the hepatic TG levels. Animals fed the alcohol diet consumed only small amounts of carbohydrate for long periods of time. Since the inclusion of glucose or its metabolites in the alcohol diet fed to rats caused a marked decrease in the liver TG content, it is likely that the production or prevention of fatty liver is related to carbohydrate metabolism.
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PMID:Fatty liver caused by chronic alcohol ingestion is prevented by dietary supplementation with pyruvate or glycerol. 648 82

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

Chicks were given biotin-deficient diets containing either suboptimal (low) or supraoptimal (high) concentrations of protein from 1-d-old until they were used during their fourth week of life. The low-protein diet predisposed chicks to develop fatty liver and kidney syndrome and the high-protein diet to develop classical biotin deficiency signs. Two other groups, as controls, received biotin-supplemented rations. Low dietary protein increased lipogenesis by isolated hepatocytes but had little effect on gluconeogenesis compared to high dietary protein. Low dietary protein decreased activities of hepatic isocitrate dehydrogenase (EC 1.1.1.42), fructose-1,6-bisphosphatase (EC 3.1.3.11) and glucose-6-phosphatase (EC 3.1.3.9; GP) and increased activities of fatty acid synthase (FAS), citrate cleavage enzyme (EC 4.1.3.8; CCE) and malate dehydrogenase (decarboxylating) (EC 1.1.1.39). When biotin deficiency was superimposed, the rate of lipogenesis by isolated hepatocytes (from fed birds) was decreased. Gluconeogenesis from lactate and glycerol was also depressed. Activity of GP was further decreased by biotin deficiency on the low-protein regimen and FAS and CCE were further increased. PK activity was increased by biotin deficiency.
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PMID:The effect of biotin deficiency and dietary protein content on lipogenesis, gluconeogenesis and related enzyme activities in chick liver. 661 62

Protein kinase C (PKC) activity was evaluated and the phosphorylation of its endogenous substrates was explored in fatty liver induced by administration of ethionine (an analogue of methionine) to cows in order to assess the relevance of PKC-dependent phosphorylation in the development of fatty liver. PKC activity was decreased in both the cytosolic and the total particulate fractions from fatty livers, compared to the corresponding fractions from control liver. The mode of activation by the PKC cofactors (1-oleoyl-2-acetyl-sn-glycerol, 12-O-tetradecanoylphorbol-13-acetate, phosphatidyl-serine and Ca2+) was similar in both control and fatty livers, suggesting a quantitative but not a qualitative change in PKC in fatty liver. At least three substrate proteins (34 kDa, 26 kDa and 19 kDa) were found in the cytosolic fraction and their phosphorylation was reduced in fatty liver. These results suggest that impairment of the signal transduction pathway mediated by PKC is involved in the pathogenesis of fatty liver in cows.
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PMID:Reduced protein kinase C activity and endogenous protein phosphorylation in ethionine-induced fatty liver in cows. 770 79

To further understand the development of fatty liver during gram-negative sepsis, we measured fatty acid uptake in addition to esterification and secretion of lipids by freshly isolated hepatocytes from fasted and fed control and Escherichia coli-treated rats. Rats were made septic by intravenous (IV) injection of 8 x 10(7) live E coli colonies per 100 g body weight. For the fasted groups, food was removed after E coli injection. Fed rats received a nutritionally adequate diet intragastrically for 5 days before and 24 hours after inducing sepsis. Twenty-four hours after E coli injection, the esterification of newly synthesized fatty acids, as measured by 3H2O incorporation, and the esterification of exogenous fatty acids, measured from 14C-palmitate incorporation, into triglyceride (TG), total cholesterol, and total phospholipid phosphorus were significantly greater in hepatocytes from fasted septic rats compared with their control rats. In fed septic rats, esterification of 14C-palmitate into TG was fourfold greater than in the fed control rats. The increased rates of esterification in hepatocytes from fasted and fed septic rats were not accompanied by an increase in the labeled TG in the medium. This inability to secrete the additional TG that the hepatocytes produce resulted in a higher concentration of cellular TG in fasted and fed septic rats than in their controls. The enzymes glycerol-3-phosphate acyltransferase (GPAT) and phosphatidate phosphohydrolase (PPH) do not appear to be factors contributing to the increased TG synthesis, since the increase in enzyme activity was not accompanied by a similar increase in TG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulatory factors in the development of fatty infiltration of the liver during gram-negative sepsis. 820 57

Lipid extracts of biopsy samples from normal and non-alcohol-induced fatty human liver were studied by 1H-NMR at 200 MHz. Spectra of the lipid extracts from 10 mg samples were obtained in 6 min with routine acquisition parameters and allowed the calculation of the phosphatidylcholine to total fatty acyl chain ratio, the cholesterol to total fatty acyl chain ratio, the average fatty acyl chain length, the unsaturation ratio and the acylated glycerol to total fatty acyl chain ratio. The data suggest that lipids with a higher ratio of de novo synthesized fatty acyl chains are stored in non-alcohol-induced fatty liver. NMR lipid analysis appears to be a reliable method for the rapid assessment of hepatic lipid composition on bioptic specimens.
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PMID:1H NMR spectroscopic studies of lipid extracts from human fatty liver. 850 93

Neutral lipid storage disease (NLSD) is an autosomal recessive disorder in which excess triacylglycerol (TG) accumulates in most cells. Although it has been hypothesized that the TG accumulation is caused by a functional defect in cytosolic lipase activity, we were able to expose TG hydrolysis in NLSD cells by using triacsin C, an inhibitor of acyl-CoA synthetase that blocks the reincorporation of hydrolyzed fatty acids into glycerolipids. Our data suggest that TG lipolysis in NLSD cells is masked by rapid TG resynthesis, occurring because released acylglycerols cannot be used for phospholipid synthesis. In uptake studies, triacsin C blocked the incorporation of [3H]glycerol into glycerolipids, incorporation of [14C]oleate into TG, but not incorporation of [14C]oleate into phospholipid. Thus, the drug inhibited both de novo synthesis of glycerolipids via the glycerol-3-phosphate pathway and the synthesis of TG from diacylglycerol. The drug did not appear to block reacylation of lysophospholipids. Triacsin C caused a loss of about 60% of the TG mass from both NLSD and oleate-loaded control cells. Rates of TG lipolysis were similar in NLSD cells and oleate-loaded control cells labeled with [6-(7-nitro-2,1,3-benzoxadiazol-4-yl)-amino]hexanoic acid or labeled with [14C]oleate or [3H]glycerol and chased in the presence of triacsin C. During a 96-h chase, [14C]oleate reincorporation into the different phospholipid species increased only in control cells. Similar results were observed when NLSD, and control cells were chased after labeling with [3H]glycerol. These data strongly suggest that normal human fibroblasts mobilize stored TG for phospholipid synthesis and that recycling to PC occurs via a TG-derived mono- or diacylglycerol intermediate. Normal recycling to phosphatidylethanolamine may primarily involve TG-derived acyl groups rather than an acylglycerol precursor. NLSD cells appear to have a block in this recycling pathway with the result that both hydrolyzed fatty acids and the acylglycerol backbone are re-esterified to form TG. Because the NLSD phenotype includes ichthyosis, fatty liver, myopathy, cardiomyopathy, and mental retardation, the recycling pathway appears to be critical for the normal function of skin, liver, muscle, heart, and the central nervous system.
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PMID:Acylglycerol recycling from triacylglycerol to phospholipid, not lipase activity, is defective in neutral lipid storage disease fibroblasts. 866 20

The mechanism behind ethanol-induced fatty liver was investigated by administration of [1,1-2H2]ethanol to rats and analysis of intermediates in lipid biosynthesis. Phosphatidic acid and phosphatidylcholine were isolated by chromatography on a lipophilic anion exchanger and molecular species were isolated by high-performance liquid chromatography in a non-aqueous system. The glycerol moieties of palmitoyl-linoleoylphosphatidic acid, the corresponding phosphatidylcholine and free sn-glycerol-3-phosphate were analysed by GC/MS of methyl ester t-butyldimethylsilyl derivatives. The deuterium labelling in the glycerol moiety of the phosphatidic acid was 2-3-times higher than in free sn-glycerol-3-phosphate, indicating that a specific pool of sn-glycerol-3-phosphate was used for the synthesis of phosphatidic acid in liver. The results indicate that NADH formed during ethanol oxidation is used in the formation of a pool of sn-glycerol-3-phosphate that gives rise to triacylglycerol and possibly fatty liver.
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PMID:Coupling of ethanol metabolism to lipid biosynthesis: labelling of the glycerol moieties of sn-glycerol-3-phosphate, a phosphatidic acid and a phosphatidylcholine in liver of rats given [1,1-2H2]ethanol. 903 Jan 93

The effects of perfluorooctanoic acid (PFOA) on the levels of lipids in liver and serum were compared between mice fed a diet supplemented with soy bean oil (SO), perilla oil (PO), or fish oil (FO) for 4 weeks. Hepatic content of triglyceride (TG) was significantly lower in the mice fed the FO diet than that in the mice fed either the SO or the PO diet. The treatment with PFOA caused a marked accumulation of TG in the livers of SO-fed and PO-fed mice (seven- and twofold over their respective controls), whereas a level of TG remained low in the mice fed the FO diet. Incorporation in vivo of [3H]glycerol revealed that FO-feeding reduced synthesis of TG in the liver. The administration of PFOA increased the incorporation of [3H]glycerol into hepatic phospholipid (PL) regardless of the dietary oil, while synthesis of hepatic TG from [3H]glycerol was not altered by the treatment with PFOA. Serum level of TG was reduced by the administration of PFOA to the mice fed either the SO diet or the PO diet, while no change in the level was observed in the mice fed the FO diet. These results suggest that the accumulation of TG in the livers of PFOA-treated mice is due to the inhibition of the secretion of TG into circulation. PFOA-induced hepatic accumulation of TG is prevented by the feeding of the FO diet which inhibits TG formation. Among three dietary oils, FO-feeding alone prevented the PFOA-caused accumulation of TG in the liver. The importance of docosahexaenoic acid (22:6(n - 3)) is discussed in relation to the prevention of fatty liver induced by chemicals.
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PMID:Fish oil-feeding prevents perfluorooctanoic acid-induced fatty liver in mice. 926 1


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