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)

We reported previously that fatty liver is easily induced in a novel experimental animal, Suncus murinus (suncus) by withholding food. In this study, we focused on lipoprotein and apolipoprotein secretion from the liver. The study of lipoproteins from this animal revealed that small amounts of lipoproteins with apolipoprotein (apo) E but without apo B were observed in the fraction of density less than 1.08 g/ml. In order to learn whether apo B is synthesized by the liver or not, isolated suncus livers were perfused with an addition of [35S]methionine. Small amounts of radioactivity were observed in apo E of VLDL, and fairly large amounts in apo E and A-I in the fraction of LDL + HDL, suggesting that VLDL was secreted with apo E but not with apo B from the liver. Northern blot analysis with use of rat apo B cDNA revealed a weak signal of hybridized rat apo B cDNA between 15 kb and 9 kb in the suncus liver and intestinal mucosa; this is almost the same size as rat apo B mRNA. This finding suggests the presence of apo B mRNA in the suncus. In conclusion, apo B is not secreted from the suncus liver, owing to a defect in intracellular post-transcriptional processing or to ineffective transcription. This might be one of the reasons for fatty deposits in the suncus liver. Suncus may be a candidate for an animal model of abetalipoproteinemia as well as fatty liver due to a defect of apo B synthesis.
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PMID:Deficiency of apolipoprotein B synthesis in Suncus murinus. 178 7

Serum lipids and apolipoprotein (apo) B and A-I concentrations were determined in 164 dairy cows which had undergone liver biopsy in early lactation. The animals were divided into groups according to fatty liver severity on the basis of hepatic triglyceride content. The serum free fatty acid (FFA) concentration was higher in cows that developed fatty livers than in normal cows, and it correlated highly with liver triglycerides. Serum total cholesterol and triglyceride levels did not correlate with hepatic triglycerides. Both apo B and apo A-I levels were significantly decreased in fatty liver cows. In particular, apo B levels showed a strongly negative correlation with liver triglycerides. The present results suggest that hepatic apolipoprotein synthesis is impeded in fatty liver cows.
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PMID:Serum apolipoproteins B and A-I and naturally occurring fatty liver in dairy cows. 212 13

The relationships between fatty liver in dairy cows and reduced levels of plasma lipoproteins, and particularly of low density lipoproteins (LDL), has been previously described. Since electrophoretic heterogeneity of ultracentrifugally isolated LDL (d, 1.006-1.063 g/ml) has been found, the exact nature of this reduction in cows with fatty liver was investigated. Lipoproteins from control and severely afflicted animals were isolated by ultracentrifugation and affinity chromatography on heparin-Sepharose CL 6 B. Gradient gel electrophoresis of lipoproteins on 4-30% gels and an immunolocalization study of apoprotein A-I (apo A-I) showed that control animals have two subpopulations of apo A-I-containing particles with a mean radius of 6.52 and 5.05 nm. In the fatty liver cows, the former was clearly shifted toward smaller particles. We concluded that the depressed level and compositional modifications of LDL in severe fatty liver cows result from a decrease in the oversized apo A-I-containing lipoproteins which can be isolated in the LDL density range. This could stem from the decreased supply of triglyceride-rich lipoprotein surface components for the production of these lipoproteins. The modifications can be plausibly explained by a reduced synthesis or secretion of very low density lipoproteins (VLDL) by the liver.
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PMID:Plasma lipoproteins in dairy cows with naturally occurring severe fatty liver: evidence of alteration in the distribution of apo A-I-containing lipoproteins. 258 37

The effects of protein malnutrition (PM) followed by refeeding a balanced diet on apolipoprotein and lipid contents of the serum lipoproteins were studied in young Wistar male rats. The changes of serum apolipoproteins were compared with the appearance of fatty liver during PM and its disappearance during refeeding. The control group (T) was fed a balanced diet containing 15% casein for 42 d. Two depleted groups (C) and (G1) were fed for 28 d low protein diets containing 2% casein and 5% gluten, respectively, and then were fed the balanced diet for 14 d. During PM a concentration of triacylglycerols (TGs) in liver in the two depleted groups increased; the level in rats fed 2% casein was twice that in rats fed 5% gluten. There was a significant negative correlation between serum TGs and liver TGs. The serum apolipoproteins (apo) did not respond consistently. The high-density lipoproteins apo A-I, A-II and A-IV, which are more than 50% synthetized in the intestine, remained essentially unchanged, thus showing resistance to protein malnutrition. The very low density lipoproteins apo B and total apo C, which mainly originate from liver, were significantly lower in malnourished groups than in controls, while the liver TGs accumulated in malnourished groups. Only the levels of total apo C and apo B48 were correlated with hepatic TG steatosis during malnutrition and refeeding.
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PMID:Time course of changes in rat serum apolipoproteins during the consumption of different low protein diets followed by a balanced diet. 310 68

An attempt was made to mobilize adipose tissue cholesterol independently of triacylglycerol by feeding cholesterol to intact Fischer 344 rats to 'load' adipocytes followed by hypolipidemic drug treatment in order to lower plasma cholesterol and, hence, adipocyte cholesterol. In this strain of rat, body weight and adipocyte sizes remain relatively constant after 1 year of age. Therefore, alterations in adipocyte cholesterol can be ascribed to factors other than cell size. Both oxandrolone and combined cholestyramine/clofibrate treatment caused significant reductions in plasma cholesterol in cholesterol-fed rats, but cholesterol concentrations in liver were reduced only by cholestyramine/clofibrate treatment. Oxandrolone enhanced the development of liver fatty liver in the cholesterol-fed rats, but cholestyramine/clofibrate significantly reduced liver triacylglycerol concentrations. Adipocyte cholesterol in the epididymal depot was significantly elevated, not lowered, in both concentrations. Adipocyte cholesterol in the epididymal depot was significantly elevated, not lowered, in both groups of drug-treated animals. Subcutaneous adipocytes from rats receiving drug treatment also contained more cholesterol, especially in rats given oxandrolone. Increments in adipocyte cholesterol were associated with decreases in the absolute amounts of apolipoproteins, A-I and A-IV, as measured by densitometric scanning of electrophoretic gels. Under the present experimental conditions, changes in plasma cholesterol scanning of electrophoretic gels. Under the present experimental conditions, changes in plasma cholesterol concentration did not adequately reflect the cholesterol content of either liver or adipose tissue.
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PMID:Accumulation of adipocyte cholesterol during hypolipidemic drug treatment in cholesterol-fed rats. 715 Jun 24

The term lipoprotein Z (remnant-like particles) refers to lipoproteins that do not have an immunoaffinity to gel mixture of anti-apo A-I and apo B100 monoclonal antibodies (JI-H antibody). Lp Z is enriched in apo E and cholesterol esters. Quantification of this lipoprotein provides a useful index of atherogenic chyromicron and VLDL remnant particles. Serum concentration of this lipoprotein is well correlated to serum triglycerides in normal subjects and patients with hypertriglyceridemia, and to serum LDL-cholesterol in normal subjects. The normal range of this lipoprotein is below 5 mg/dl and the increased serum concentration is often observed in ischemic heart disease, diabetes mellitus, hypertriglyceridemia and fatty liver.
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PMID:[Lipoprotein Z]. 785 93

Fatty liver disease (FLD) characterised by a high plasma levels of lipoproteins and remnant-like lipoproteins (RLP) is a risk factor for impaired microvascular blood flow, endothelial cell dysfunction and atherosclerosis. Using an immunoseparation technique with a gel mixture containing human monoclonal antibodies to apo A-I and apo B-100, we separated and measured RLP cholesterol (RLP-C) levels which reflect RLP in patients with FLD (n=20). Whole blood transit time (TT) was determined by a microchannel method (MC-FAN) which allows blood flow to be viewed via a microscope connected to an image display unit. RLP-C levels were higher (P<0.01) in FLD, 15.6 +/- 1.0 mg/dl compared with 4.8 +/- 0.5 mg/dl for controls (n=20). Similarly, TT was longer (P<0.01) in FLD, 284.5 +/- 26.1 sec/100 microl compared with 82.8 +/- 1.0 sec/100 microl for controls. Since the liver is a major site for RLP formation and degradation, it is affected to a greater extent in patients with FLD. It is likely that high levels of RLP can impair microvascular perfusion in the liver tissue and contribute to the development and progression of FLD.
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PMID:Impaired blood rheology by remnant-like lipoprotein particles: studies in patients with fatty liver disease. 1156 10

The liver constitutes the first barrier in the control of hematogenous dissemination for Candida albicans of intestinal origin. The ability of this organ to limit the growth of the yeast and to mount an efficient inflammatory reaction is crucial in determining the outcome of the fungal infection. When rats infected with C. albicans are exposed to chronic varied stress, the cell recruitment is impaired at the site of the infection, the tissue reaction is highly disorganized in target organs and the infection evolution is more severe. At hepatic level, higher fungal burden is associated with hyphal form and the consistent presence of steatosis (fatty liver). Herein we aimed at characterizing the steatosis associated with C. albicans infection and to provide molecular evidence of the correlation among liver injury markers, stress products and the initiation of the inflammatory tissue reaction. After 3 days of stress and infection, we observed micro and macro steatosis in acinar zone 1 (specific lipid stain), higher lipid peroxidation and increased levels of serum alanine aminotransferase and gamma glutamil transferase. While infection triggered hepatic NO production and arginase activity, stress down-modulated both. Remarkably, defects in levels of TNF-alpha and NO were observed during the first step of the inflammatory response. Our results demonstrate that stress mediators down-regulate the acute inflammatory reaction in the hepatic scenario, promoting a major liver injury with particular immunopathological traits.
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PMID:High dissemination and hepatotoxicity in rats infected with Candida albicans after stress exposure: potential sensitization to liver damage. 1552 22

Hyperhomocysteinemia has long been associated with atherosclerosis and thrombosis and is an independent risk factor for cardiovascular disease. Its causes include both genetic and environmental factors. Although homocysteine is produced in every cell as an intermediate of the methionine cycle, the liver contributes the major portion found in circulation, and fatty liver is a common finding in homocystinuric patients. To understand the spectrum of proteins and associated pathways affected by hyperhomocysteinemia, we analyzed the mouse liver proteome of gene-induced (cystathionine beta-synthase (CBS)) and diet-induced (high methionine) hyperhomocysteinemic mice using two-dimensional difference gel electrophoresis and Ingenuity Pathway Analysis. Nine proteins were identified whose expression was significantly changed by 2-fold (p < or = 0.05) as a result of genotype, 27 proteins were changed as a result of diet, and 14 proteins were changed in response to genotype and diet. Importantly, three enzymes of the methionine cycle were up-regulated. S-Adenosylhomocysteine hydrolase increased in response to genotype and/or diet, whereas glycine N-methyltransferase and betaine-homocysteine methyltransferase only increased in response to diet. The antioxidant proteins peroxiredoxins 1 and 2 increased in wild-type mice fed the high methionine diet but not in the CBS mutants, suggesting a dysregulation in the antioxidant capacity of those animals. Furthermore, thioredoxin 1 decreased in both wild-type and CBS mutants on the diet but not in the mutants fed a control diet. Several urea cycle proteins increased in both diet groups; however, arginase 1 decreased in the CBS(+/-) mice fed the control diet. Pathway analysis identified the retinoid X receptor signaling pathway as the top ranked network associated with the CBS(+/-) genotype, whereas xenobiotic metabolism and the NRF2-mediated oxidative stress response were associated with the high methionine diet. Our results show that hyperhomocysteinemia, whether caused by a genetic mutation or diet, alters the abundance of several liver proteins involved in homocysteine/methionine metabolism, the urea cycle, and antioxidant defense.
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PMID:The nutrigenetics of hyperhomocysteinemia: quantitative proteomics reveals differences in the methionine cycle enzymes of gene-induced versus diet-induced hyperhomocysteinemia. 2000 33

Obesity-related pathologies, such as nonalcoholic fatty liver disease, are linked to mitochondrial dysfunction and nitric oxide (NO) deficiency. Herein, we tested the hypothesis that a high-fat diet (HFD) modifies the liver mitochondrial proteome and alters proteins involved in NO metabolism, namely arginase 1 and endothelial NO synthase. Male C57BL/6 mice were fed a control or HFD and liver mitochondria were isolated for proteomics and reactive oxygen species measurements. Steatosis and hepatocyte ballooning were present in livers of HFD mice, with no pathology observed in the controls. HFD mice had increased serum glucose and decreased adiponectin. Mitochondrial reactive oxygen species was increased after 8 weeks in the HFD mice, but decreased at 16 weeks compared with the control, which was accompanied by increased uncoupling protein 2. Using proteomics, 22 proteins were altered as a consequence of the HFD. This cohort consists of oxidative phosphorylation, lipid metabolism, sulfur amino acid metabolism, and chaperone proteins. We observed a HFD-dependent increase in arginase 1 and decrease in activated endothelial NO synthase. Serum and liver nitrate + nitrite were decreased by HFD. In summary, these data demonstrate that a HFD causes steatosis, alters NO metabolism, and modifies the liver mitochondrial proteome; thus, NO may play an important role in the processes responsible for nonalcoholic fatty liver disease.
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PMID:Chronic exposure to a high-fat diet induces hepatic steatosis, impairs nitric oxide bioavailability, and modifies the mitochondrial proteome in mice. 2091 31


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