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)

Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VLDL) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL, secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [(3)H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apoVLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are separated by polyacrylamide gel electrophoresis. Similar patterns are noted when non-recirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation.
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PMID:Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats. 22 14

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

In a previous report (Langner, C. A., Birkenmeier, E. H., Ben-Zeev, O., Schotz, M. C., Sweet, H. O., Davisson, M. T., and Gordon, J. I. (1989) J. Biol. Chem. 264, 7994-8003), we characterized the early developmental phenotype of mice that were homozygous for the autosomal recessive fatty liver dystrophy (fld) mutation. Shortly after birth, these mice can be distinguished from their +/? littermates by large pale livers, hypertriglyceridemia, elevations in hepatic apolipoprotein A-IV and apoC-II mRNA levels, and tissue-specific decreases in lipoprotein lipase and hepatic lipase activities. These traits resolve by the early weaning period. We have now characterized a second feature of this mutation: a peripheral neuropathy that becomes manifest by an abnormal gait at the end of the second postnatal week and persists through adulthood. Electron microscopic studies of sciatic nerves from 4-day-to 1-year-old fld/fld mice demonstrated a variety of abnormalities including thin, poorly compacted myelin sheaths, active myelin breakdown, and enlarged Schwann cell mitochondria and nuclei. Western blot analysis of sciatic nerve homogenates prepared from 1 to 3-month-old fld/fld mice and their +/? littermates indicated that homozygous animals have striking reductions in two peripheral nerve myelin-associated proteins, P0 and P2. The steady-state level of apoE, a protein induced during nerve regeneration, is markedly elevated. Furthermore, two axon-specific proteins, neurofilament 68K and growth-associated 43 protein, display altered expression in adult fld/fld sciatic nerves. High performance thin-layer chromatography revealed deficiencies in phospholipids, glycosphingolipids, and some neutral lipids in fld/fld sciatic nerves harvested during the first several months of life (compared to their +/? littermates). Cholesterol esters were elevated in homozygotes. By contrast, no differences in brain lipids were noted between fld/fld animals and their +/? littermates. These data suggest that the fld mutation is associated with an abnormality of myelin formation (dysmyelination) as well as demyelination and axonal degeneration that persists despite apparent resolution of the neonatal hypertriglyceridemia and associated lipase abnormalities. These findings establish the fld/fld mouse as an excellent model system for analyzing homeostatic mechanisms that modulate lipid metabolism in newborn mice and for examining the pathogenesis of peripheral neuropathies associated with dyslipidemias.
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PMID:Characterization of the peripheral neuropathy in neonatal and adult mice that are homozygous for the fatty liver dystrophy (fld) mutation. 205 Jun 89

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

Recently numerous reports show deleterious effects of alcohol abuse on pregnant women giving their children a high risk of stillbirth and/or several developmental abnormalities and mental retardation, i.e. the Fetal alcohol syndrome (FAS). In the present study, the effects of maternal alcohol consumption on lipid metabolism in the litter liver were investigated in rats. These rats showed not only quite less lipid deposition in spite of large amount of alcohol consumption up to adulthood, but also showed increased FFA oxidation in the livers. In addition, increased level of very low density lipoprotein and hypoglucagonemia were found. 40 micrograms/kg of glucagon which is known as an inhibitory factor of apoprotein production in the liver, was injected for 2 weeks into the rat tail vein and resulted in apparent fatty liver and hypolipoproteinemia. Norepinephrine injection (1 mg/kg) caused plasma glucagon to be depressed in the rat as compared with adult alcohol rats. Plasma cyclic AMP response to glucagon was also depressed in these rats. From these results, it is suggested that the deranged glucagon secretion from the pancreas and lowered glucagon-induced cyclic AMP response would relate to the abnormal lipoprotein metabolism in the rat.
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PMID:[Experimental studies on lipoprotein metabolism in rats reared with liquid alcohol diet from the fetal life]. 298 81

We describe a child, the issue of phenotypically normal parents, who had fat malabsorption, both intestinal and hepatic steatosis, and serum cholesterol and triglyceride concentrations of 38 and 63 mg/dl, respectively. Lipoprotein electrophoresis, Ouchterlony double diffusion, and electron microscopy demonstrated that normal low density lipoproteins (LDL: 1.006 less than rho less than 1.063 g/ml) were absent. Lipoprotein particles in the rho less than 1.006-g/ml fraction were triglyceride rich, very large (93.2 +/- 35.1 nm), and contained the B-48 but not the B-100 apoprotein; both species of apolipoprotein (apo) B were found in the parents' lipoproteins. These chylomicrons and chylomicron remnants were present even in the patient's fasting plasma, which suggested prolonged dietary fat absorption. Plasma levels of high density lipoprotein lipids and proteins were low, and the phosphatidylcholine/sphingomyelin ratio was reduced as in typical abetalipoproteinemia. The monosialylated form of apo C-III was not identified on polyacrylamide gel electrophoresis, which suggested that this protein was elaborated only with very low density lipoproteins (VLDL). A radioimmunoassay for apo B employing a polyclonal antisera to plasma LDL gave apparent plasma apo B levels of 0.6, 66, and 57 mg/dl in the patient and his father and mother, respectively. The displacement curve generated by the parents' VLDL and LDL did not did not differ from control lipoproteins. The patient's chylomicron-chylomicron remnant fraction displaced normal LDL over the entire radioimmunoassay range, but the efficiency of displacement was strikingly less than with B-100 containing lipoproteins. If the patient's B-48 protein is not qualitatively abnormal, these results confirm very limited immunochemical cross-reactivity between at least one major epitope on B-100 and the epitopes expressed on B-48. The apo B defect in this patient appears to be recessive. It abolishes B-100 production and may additionally limit the formation of B-48.
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PMID:Apolipoprotein B-100 deficiency. Intestinal steatosis despite apolipoprotein B-48 synthesis. 403 Oct 57

This study provides confirmation of previous observations that showed that rats fed a diet containing 1% orotic acid for 7 days develop a fatty liver and that there is an inhibition of the secretion of low density lipoproteins without altering general liver protein synthesis. Accumulated fat droplets (liposomes) are entrapped within rough endoplasmic reticulum vesicles. In this study, these vesicles have been shown to accumulate the apolipoproteins of low and very low density lipoproteins. Inhibition of lipoprotein secretion was demonstrated by perfusion of livers from orotic acid-fed rats with a serum-free medium. Liposomes were isolated from these rats. Partially delipidated liposomes, but not similarly treated microsomes or cell sap, were found to form a precipitation line when reacted against anti-low density lipoprotein antiserum. Detergent solubilization of the liposome followed by density gradient centrifugation resulted in a peak at d 1.025 g/ml containing both lipid and protein. Acrylamide electrophoresis in 8 m urea after total delipidation demonstrated liposomal bands which coelectrophoresed with three of four very low density lipoprotein bands; there was no band corresponding to the very low density lipoprotein band which travels furthest in acrylamide electrophoregrams. However, acrylamide electrophoresis of the apoproteins of serum high density lipoprotein from orotic acid-fed animals revealed the presence of the latter band. The results indicate that liver liposomes from orotic acid-fed rats apparently contain the low density apoprotein and probably several other very low density lipoprotein peptides.
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PMID:Serum lipoprotein accumulation in the livers of orotic acid-fed rats. 436 41

The lipids and apoproteins of serum, hepatic Golgi cisternae, and secretory vesicle lipoproteins from hypothyroid, hypercholesterolemic rats were analyzed and compared to homologous lipoprotein fractions from euthyroid rats fed a low fat chow diet in order tao determine the nature of the nascent lipoprotein particles and indicate post-secretory modifications. Normal rat hepatic Golgi and secretory vesicles contained predominantly triglyceride-rich very low density lipoprotein (VLDL) which had little associated apoC-II or C-III and was deficient in apoE when compared to serum VLDL. Small quantities of cholesteryl ester-enriched low density lipoprotein (LDL) containing apoB and apoE were also present. Hepatic fractions from hypercholesterolemic rats contained cholesteryl ester- and apoE-rich, triglyceride-depleted VLDL of similar size, immunodiffusion characteristics, ratio of immunoassayable apoB to apoE, and lipid composition, to hypercholesterolemic serum VLDL. Hepatic levels of LDL in hypercholesterolemic rats were markedly elevated and enriched in cholesteryl ester and apoE when compare to normal hepatic LDL. Cholesteryl ester-rich hepatic VLDL and LDL increased in size and in cholesteryl ester and apoE content during transit from the Golgi cisternae into the secretory vesicles. Triglyceride-rich VLDL only acquired apoE which was further supplemented upon secretion. Nascent VLDL and LDL represented LpB-LpE association complexes and no deficiency in any apoE isoprotein within the cholesteryl ester-rich serum lipoproteins was observed. Thus, dietary-induced hypercholesterolemia in hypothyroid rats results in a fatty liver whose lipoprotein secretory products contribute to the plasma pool of abnormal cholesteryl ester- and apoE-enriched lipoproteins.
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PMID:Serum and hepatic nascent lipoproteins in normal and hypercholesterolemic rats. 679 11

Excessive alcohol ingestion results in profound derangements of lipid and lipoprotein metabolism, reflecting the effects of ethanol on peripheral and hepatic lipid metabolism and its toxic effects on hepatic function. The alterations in plasma lipids and lipoproteins are secondary to complex abnormalities of lipoprotein synthesis, secretion and catabolism. The major effects of alcohol include fatty liver secondary to excessive triglyceride synthesis, resulting in an imbalance between synthesis and hepatic secretion; hypertriglyceridemia and hypercholesterolemia; defective plasma cholesterol esterification; and decreased high-density lipoprotein cholesterol. In patients with severe alcoholic hepatitis, the plasma lipoproteins have an abnormal structure and apoprotein composition. Although these changes are usually reversible with abstinence from alcohol (if liver function returns to normal), they indicate serious effects of alcohol on the liver, which may culminate in cirrhosis and hepatic insufficiency. These effects of alcohol on lipids and lipoproteins should be contrasted with the elevation in high-density lipoprotein cholesterol concentration produced by moderate alcohol intake and the possibility that this increase may protect against the development of atherosclerotic disease.
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PMID:Lipid and lipoprotein abnormalities in alcoholic liver disease. 702 Sep 88

An ELISA was developed to evaluate the concentration of apolipoprotein A-I, a major apoprotein in high-density lipoprotein, in the serum of cattle. Serum apolipoprotein A-I was purified electrophoretically, and antibodies to this protein were raised in rabbits. The specificity of the antiserum was assessed by use of several immunologic techniques including western blotting. The ELISA was sensitive (detection limit was 70 ng of apolipoprotein A-I/ml) and reliable (coefficients of variance were in the range of 3.5 to 8.2%). By use of this method, the serum apolipoprotein A-I concentration was higher in 2- to 6-year-old Holstein cows (mean +/- SD, 0.580 +/- 0.304 mg/ml) than in 7- to 15-month-old heifers (0.339 +/- 0.237 mg/ml), 6-month-old heifers (0.238 +/- 0.188 mg/ml), and 6-month-old steers (0.173 +/- 0.146 mg/ml). The concentration, however, is not largely different in cows in early, middle, and late lactation and in non-lactating stages. Results also indicated that apolipoprotein A-I concentration was decreased in cows with hepatic lipidosis (fatty liver) induced by administration of ethionine, suggesting that this method is a useful tool for the pathophysiologic study of lipid metabolism and its impairment in cattle.
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PMID:Enzyme-linked immunosorbent assay for apolipoprotein A-I in the serum of cattle. 778 12


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