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

Ethionine, an analogue of methionine, induces fatty liver in rats by inhibiting protein synthesis, including that of apolipoproteins in liver. Ethionine was administered to cows to elucidate the participation in fatty liver development of impaired triglyceride secretion from liver attributable to decreased apolipoprotein synthesis. The administration resulted in a significant increase of liver triglyceride contents. Several apolipoproteins were found to have decreased concentrations. In particular, apolipoprotein B-100 in very low-density (0.95 to 1.006 g/ml) lipoprotein and in low-density (1.006 to 1.063 g/ml) lipoprotein fractions was greatly reduced. The decreases of apolipoprotein B-100 concentrations in the 2 lipoprotein fractions were at least partly correlated to the decreased triglyceride concentrations in the respective fractions. Decreased concentrations of apolipoprotein A-I in high-density (1.063 to 1.210 g/ml) lipoprotein were also observed, although not as distinctly as with apolipoprotein B-100. Total cholesterol and phospholipid concentrations in low- and high-density lipoprotein fractions were decreased. The decrease in cholesterol was attributed to reduced concentrations of cholesteryl esters. It was suggested that the impaired lipid secretion from liver attributable to the decreased apolipoprotein concentrations has a role in ethionine-induced fatty liver of cows.
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PMID:Induction of fatty liver in cows by ethionine administration and concomitant decreases of serum apolipoproteins B-100 and A-I concentrations. 146 99

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

The complex distribution of polychlorinated biphenyl (PCB) isomers and congeners amongst plasma fractions of the pigeon suggests that the lipid and apolipoprotein components of lipoproteins, as well as plasma proteins, may be important in transporting PCBs to tissues (Borlakoglu et al., Biochem. Pharmac. 40, 265 (1990]. Pigeons were injected with the commercial PCB mixture Aroclor 1254 (1.5 mmol/kg body weight). After 120 hr triacylglycerol-like droplets accumulated in hepatocytes ('fatty liver syndrome'), there was proliferation of the hepatic smooth endoplasmic reticulum, and plasma concentrations of triacylglycerol and total cholesterol increased. This was accompanied by significant decreases in plasma concentrations of total protein, total apolipoproteins of the low density lipoprotein (LDL) and the high density lipoprotein (HDL) fractions, and albumin and by a significant increase in that of urea, indicating increased protein breakdown. These results suggest that Aroclor 1254 increased hepatic lipid synthesis, but decreased hepatic production of albumin and apolipoproteins. This would explain the accumulation of triacylglycerol in the liver and the increase in the proportion of triacylglycerol to apolipoprotein in the total lipoproteins. From the evidence presented, a model is proposed based on the association of PCBs with hydrophobic domains of lipids and proteins for the transport of PCBs by plasma fractions, their uptake into cells and intracellular metabolism, and their accumulation in adipose tissue.
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PMID:Transport and cellular uptake of polychlorinated biphenyls (PCBs)--II. Changes in vivo in plasma lipoproteins and proteins of pigeons in response to PCBs, and a proposed model for the transport and cellular uptake of PCBs. 211 78

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

An autosomal recessive mutation, termed fatty liver dystrophy (fld), can be identified in neonatal mice by their enlarged and fatty liver (Sweet, H. O., Birkenmeier, E. H., and Davisson, M. T. (1988) Mouse News Letter 81, 69). We have examined the underlying metabolic abnormalities in fld/fld mice from postnatal days 3-40. Serum and hepatic triglyceride levels were elevated 5-fold in suckling fld/fld mice compared to their +/? littermates but abruptly resolved at the suckling/weaning transition. Blot hybridization analysis of liver and intestinal RNAs revealed a liver-specific increase in apolipoprotein (apo) A-IV and C-II mRNA concentrations (100- and 6-fold, respectively) that was limited to the suckling and early weaning stages in fld/fld mice. Resolution of these differences during the weaning period could not be delayed by prolonging suckling to the 20th postnatal day nor could the mutant phenotype be elicited in young adult animals with a high fat diet. Lipoprotein lipase (LPL) activity was reduced 16-fold in the white adipose tissue of fld/fld mice until the onset of weaning. Heart activity was decreased less than 2-fold, but there were no deficits in brown adipose tissue or liver. Hepatic lipase (HL) mRNA levels and activity were significantly reduced in fld/fld livers and sera, respectively, during the suckling period. Mapping studies show the fld locus to be distinct from loci encoding LPL, HL, and apoA-IV, and those responsible for the combined lipase deficiencies in cld/cld and W/Wv mice. These data suggest that the fld mutation is associated with developmentally programmed tissue-specific defects in the neonatal expression of LPL and HL activities and provide evidence for a new regulatory locus which affects these lipase activities. This mutation could serve as a useful model for (i) analyzing the homeostatic mechanisms controlling lipid metabolism in newborn mice and (ii) understanding and treating certain inborn errors in human triglyceride metabolism.
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PMID:The fatty liver dystrophy (fld) mutation. A new mutant mouse with a developmental abnormality in triglyceride metabolism and associated tissue-specific defects in lipoprotein lipase and hepatic lipase activities. 272 72

Thirteen members of a family carrying a gene for pedigree of hypobetalipoproteinemia were analyzed for lipoprotein compositions, apolipoprotein (apo) B levels, and apo B isoforms. Judging from low density lipoprotein (LDL)-cholesterol (Chol) and apo B levels, a 75-year-old proband, a father who died of unknown fever, thrombopenia, and anemia, and his wife were heterozygous for hypobetalipoproteinemia. The proband had ataxic movement of hands and gait disturbance in later life. Three of four living siblings had extremely low levels of LDL-Chol (6 mg/dL) and LDL-apo B (2 mg/dL), and were postulated to have homozygous hypobetalipoproteinemia. Electrophoresis revealed marked deficiency of apo B-100, although trace amounts were noted in LDL. In contrast, apo B-48 was present in chylomicrons obtained after a fatty meal in the two patients with homozygous hypobetalipoproteinemia, indicating a selective deficiency of apo B-100 but not apo B-48. The defect in these patients seemingly is different from abnormal apo B-37 reported recently for a family with hypobetalipoproteinemia. Clinically, acanthocytotic red blood cells (8% to 12%), fatty liver, and low levels of serum lipid-soluble vitamins A and D were noted in homozygotes. One heterozygous sibling had 26 mg/dL LDL-Chol and 5 mg/dL LDL-apo B levels. All seven subjects in the third generation had low levels of Chol (85 to 140 mg/dL), LDL-Chol (40 to 63 mg/dL) and LDL-apo B (10 to 20 mg/dL). They also showed mild acanthocytosis (0.5% to 2%) and a decrease of fat-soluble vitamins in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Homozygous hypobetalipoproteinemia with spared chylomicron formation. 290 27

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

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

The purpose of this work was to study if the steatogenic effect on the liver of Rifampicin, which is an inhibitor of the RNA polymerases DNA dependent in bacteria, can be prevented by an anabolic steroid: 19 nortestosterone phenylproprionate (19-NTPP) which probably stimulates the RNA polymerase activity in eukariotic cells. 19-NTPP (25 mg/kg/24 h, i.p.) was administered to male and both intact and ovariectomized female rats for 8 days prior to the administration of Rifampicin (400 mg/kg/24 h for 8 days). In male rats, 19-NTPP does not prevent the Rifampicin-induced fatty liver. On the contrary, in female rats, 19-NTPP exerts a partial protective effect in intact as well as in ovariectomized animals. These results show that the protective effect of 19-NTPP against Rifampicin fatty liver is less complete and little specific, comparated to the protective effect obtained against another steatogenic compound in female rats: alpha-Amanitin, which is a potent inhibitor of RNA polymerase II in eukariotic cells. In conclusion, the inhibitor effect of Rifampicin on the hepatic apolipoprotein biosynthesis appears as less specific and more intricate than the comparable effect of alpha-Amanitin.
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PMID:Study of the protective effect of an anabolic steroid, 19-nortestosterone phenylpropionate (19-NTPP) on the fatty liver induced by high doses of rifampicin in the rat. 693 30


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