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)

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

Ethionine, an ethyl analogue of methionine, induces fatty liver in rats. The effects of ethionine administration on protein kinase C (PKC) in rat liver was examined. By a single administration at a dose of 0.5 mg/g body wt., liver PKC activity was increased in both cytosolic and total particulate fractions. The increase in cytosol was significant, even at 4 h after administration, when compared with control rat liver cytosol. On the other hand, a 4-day consecutive administration (0.5 mg/g per day) resulted in decreased PKC activity, particularly in cytosol, when compared with the control. Protein phosphorylation in liver catalyzed by PKC was found to be enhanced by ethionine, irrespective of the mode of administration. The enhanced phosphorylation was observed in both cytosolic and total particulate fractions. The change of PKC activity, and the phosphorylation of its endogenous substrates, are postulated to be involved in the pathogenesis of ethionine-induced fatty liver of rats.
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PMID:Altered protein kinase C activity and its endogenous protein phosphorylation in rat liver after administration of ethionine. 160 39

Ethionine, a methionine analogue, induces fatty liver in rats. The mechanism by which ethionine induces fatty liver is thought to be due to the inhibition of synthesis of very-low-density lipoprotein. Since the synthesis of lipoprotein is correlated with liver estradiol receptor concentrations, we examined the effect of ethionine on estradiol receptor concentrations in rat liver. Estradiol receptor concentrations in both cytosolic and nuclear fractions were greatly decreased by a single injection of ethionine at a dose of 0.5 mg/g body wt. In particular, the decrease in nuclear receptor concentrations was observed a few hours after the injection and correlated with the decrease in triglyceride content in the very-low-density lipoprotein fraction. These results suggest that liver estradiol receptor is involved in the pathogenesis of ethionine-induced fatty liver of rats.
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PMID:Decreased estradiol receptor concentrations in ethionine-induced fatty liver of rats. 195 23

Changes of enzymes involved in the hepatic metabolism of long-chain fatty acids (palmitoyl-CoA synthetase (EC 6.2.1.3), carnitine palmitoyltransferase (EC 6.2.1.3), glycerophosphate acyltransferase (EC 2.3.1.15)) in the liver of male rats were examined after ethionine exposure. Ethionine administration resulted in a dose- and time-dependent enhancement of the palmitoyl-CoA synthetase activity both in the mitochondrial, peroxisomal and microsomal fractions. The total carnitine palmitoyltransferase activity in the mitochondrial fraction was enhanced. Ethionine administration was also associated with dose- and time-dependent changes of the microsomal glycerophosphate acyltransferase activity, whereas the mitochondrial enzyme activity was marginally affected. The hepatic triacylglycerol content of the ethionine-treated animals was increased. Hepatic lipids were accumulated in large droplets. Serum triacylglycerol and cholesterol were decreased. In particular, the serum HDL-cholesterol level was lowered. The concentration of ATP in the liver decreased. Accumulation of the metabolic product S-adenosylethionine (AdoEth) was observed for the first 2 days of exposure followed by a fall in S-adenosylmethionine (Ado-Met) during the next 10 days. Linear regression analysis of ATP content versus AdoEth and AdoMet showed highly significant correlations. A significant correlation between the hepatic triacylglycerol and AdoEth content was also observed upon ethionine treatment. The data show that ethionine perturbs the hepatic lipid metabolism. Enhanced esterification of long-chain fatty acids, but not a simple reduction of their oxidation, might contribute to ethionine-induced fatty liver in addition to a block in secretion of lipoproteins and decreased protein synthesis.
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PMID:Ethionine-induced alterations of enzymes involved in lipid metabolism and their possible relationship to induction of fatty liver. 297 12

Female NMRI mice were fed diets containing l-ethionine (0.1 and 0.3% w/w) and phenylalanine (3% w/w), as well as respective control diets. Ethionine, the S-ethylated analog of methionine, was shown to inhibit phenylalanine hydroxylase in vivo, whereby in vitro kinetics remained unaffected. Treatment with ethionine resulted in fatty liver, reduced ATP content of liver, and alterations in serum amino acid concentrations. In the high dosage ethionine group, for instance, concentrations of Ala, Gly, Ser, Met, and Phe were increased whereas concentrations of Lys, Asp, and Pro were decreased. Applying ethionine together with phenylalanine resulted in hyperphenylalaninemia and phenylketonuria. Feeding phenylalanine alone also led to decreased activity of phenylalanine hydroxylase and increased concentration of Phe in serum. Ethionine only had a minimal effect on body weight gain; however, the hyperphenylalaninemic condition induced by application of the high dosage of ethionine and phenylalanine induced severe loss of body weight. A disturbed protein synthesis and protein phosphorylation might be the underlying mechanism of ethionine-induced suppression of phenylalanine hydroxylase.
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PMID:Induction of hyperphenylalaninemia in mice by ethionine and phenylalanine. 374 96

Progenitors regenerate fatty livers but the mechanisms involved are uncertain. The Hedgehog pathway regulates mesendodermal progenitors and modulates mesenchymal-epithelial interactions during tissue remodeling. To determine if Hedgehog signaling increases in liver progenitors during fatty liver injury, we compared expression of Hedgehog ligands and target genes across a spectrum of injury. Leptin-deficient ob/ob mice with fatty livers and their healthy lean littermates were studied before and after exposure to the hepatotoxin, ethionine. At baseline, ob/ob mice had greater liver damage than controls. Ethionine induced liver injury in both ob/ob and lean mice, with greater injury occurring in ob/ob mice. After ethionine, the ob/ob mice developed liver atrophy and fibrosis. Liver injury increased hepatic accumulation of progenitors, including ductular cells that produced and responded to Hedgehog ligands. A dose-response relationship was demonstrated between liver injury and expansion of Hedgehog-responsive progenitors. In severely damaged, atrophic livers, nuclei in mature-appearing hepatocytes accumulated the Hedgehog-regulated mesenchymal transcription factor, Gli2 and lost expression of the liver epithelial transcription factor, hepatocyte nuclear factor 6 (HNF-6). Hepatic levels of collagen mRNA and pericellular collagen fibrils increased concomitantly. Hence, fatty liver injury increases Hedgehog activity in liver progenitors, and this might promote epithelial-mesenchymal transitions that result in liver fibrosis.
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PMID:Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice. 1795 94