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 report the free, acyl-, and total carnitine contents of 49 clinically healthy volunteers and 167 chronic alcoholics with various clinically and/or anatomopathologically identified degrees of hepatic affection. There was a gradual upward trend in carnitine levels as the degree of hepatic affection increased. In cirrhotic patients, both free and acylcarnitine levels were significantly higher than normal, but there was no systematic hypercarnitinemia in other stages of alcoholism; on the contrary, noncirrhotic alcoholic patients accounted for 82.6% of all hypocarnitinemia cases. Hypercarnitinemia among cirrhotic alcoholics was due chiefly to increased free carnitine concentrations. Acylcarnitine levels in patients with hepatic steatosis were significantly higher than those in normal subjects (P less than 0.001), but there were no other statistically significant differences in either acyl- or free carnitine levels between normals on the one hand and, on the other, patients with hepatic steatosis, alcoholic hepatitis, slight hepatopathy, or chronic hepatopathy without portal hypertension.
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PMID:Free carnitine and acylcarnitine levels in sera of alcoholics. 239 Feb 92

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

Trimethyltin (TMT) is a potent neuronotoxiciant but there is little data regarding its systemic effects. In this study, female BALB/c mice were administered either 0.9% saline or 2.75 mg TMT/kg intraperitoneally (i.p.). The animals were then housed in room air or in glass chambers flushed with either 10%, 40%, or 100% oxygen. Mice were sacrificed at 4, 8, 24, and 48 h after treatment and adrenals analyzed for various neurotransmitters by ion-pairing HPLC with electrochemical detection. In addition, adrenal S-adenosylmethionine (SAM) and blood ketone bodies were determined Sections of adrenals were evaluated by electron microscopy for histopathological changes. In vivo treatment with the toxicant resulted in a significant decrease in adrenal epinephrine and norepinephrine levels as early as 8 h following treatment. This effect preceded the appearance of both clinical signs and histopathological changes in the hippocampus by 12-24 h. With exposure to TMT in room air, mouse adrenal content of epinephrine fell from 1861.3 +/- 97.3 ng/4 mg to 1493.3 +/- 137.0 ng/4 mg while norepinephrine levels fell from 779.6 +/- 32.3 ng/4 mg to 503.4 +/- 44.3 ng/4 after 8 h. Supplementation with 40% oxygen did not attenuate this effect but in the case of mice treated with TMT and housed in 100% oxygen for 48 h, actually exacerbated the adrenal epinephrine depletion. Housing in approximately half normal atmospheric oxygen (10%) neither prevented nor enhanced the effects of TMT. The epinephrine/norepinephrine ratios were: control, 2.44; TMT (room air), 1.56; TMT (10% O2), 1.72; TMT (40% O2), 1.44; TMT (100% O2), 1.07. None of the conditions used in this study caused a decrease in adrenal dopamine, 5-hydroxyindole acetic acid (5-HIAA), 5-hydroxytryptamine (5-HT) or in the level of SAM. TMT treatment significantly increased blood ketone bodies indicating additional metabolic dysfunction. The significance of these findings in relation to TMT neuronotoxicity and fatty liver syndrome are discussed.
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PMID:Trimethyltin as a selective adrenal chemosympatholytic agent in vivo: effect precedes both clinical and histopathological evidence of toxicity. 372 95

In view of the protective effects of SAM on alcohol-induced fatty liver degeneration, an investigation has been carried out to see if this compound accelerates the clearance of ethanol and acetaldehyde in humans. Both parameters were significantly lower after SAM, indicating the capability of exogenous SAM to favour the inactivation of ethanol without increasing blood levels of acetaldehyde.
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PMID:Decreased blood levels of ethanol and acetaldehyde by S-adenosyl-L-methionine in humans. 659 88

1. Rats were given a purified folate-deficient diet containing 5 g succinylsulphathiazole/kg for 4-5 months in two experiments. Control rats were supplemented with folic acid in the drinking-water. 2. Weight gain was much below normal in the folate-deprived rats after the first month. Very low folate levels were recorded in blood, liver and peripheral nerve (12-33% of control). In the central nervous system, including the cerebrospinal fluid, the folate depletion was less conspicuous (50-80% of control). Only marginal signs of anaemia were found and no signs of neurological dysfunction were detected, using nerve conduction velocity measurement and co-ordination tests. 3. Light and electron microscopy of the folate deficient liver revealed fatty infiltration, and enlargement of liver parenchymal cells, nuclei and nucleoli. There was often a considerable amount of bile ductular cells in the lobuli but no cirrhosis. The morphological changes resembled those observed in choline deficiency. 4. Phospholipid N-methylation in liver was depressed in folate-deficiency. This was probably due to a decreased availability of S-adenosylmethionine caused by the low concentrations of methylated folate in liver. Intraperitoneal administration of methionine did not normalize phospholipid methylation. 5. In folate deficiency the proportion of ethanolamine phosphoglyceride in liver was increased at the expense of choline phosphoglyceride, which is consistent with a decreased phospholipid methylation. Also an increase in liver triacylglycerol was noted, in accordance with the morphological observations. Brain lipid composition was unchanged. 6. After the injection of labelled ethanolamine, isotope accumulated in liver phosphoethanolamine in folate deficiency, probably due to an impairment of the CTP:ethanolaminephosphate cytidylyltransferase (EC 2.7.7.14) reaction. The mechanism of this impairment is discussed. 7. Although the low concentrations of folate was the main nutritional change in the deprived animals, changes with respect to vitamin B12 and maybe also choline cannot be excluded. We conclude that some of the changes in folate deficiency, i.e. fatty liver and decreased biosynthesis of liver phospholipids may be due to a precipitated deficiency of lipotropic agents, whereas other differences may be specific for deficiency of folate per se, such as changes in liver phospholipid fatty acids and some of the morphological aberrations.
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PMID:Effect of experimental folate deficiency on lipid metabolism in liver and brain. 708 22

The hypocholesterolemic action of eritadenine, a compound found in the mushroom Lentinus edodes, was investigated in relation to its influence on phospholipid metabolism in the liver of rats fed diets containing different amounts of choline chloride (0, 2 and 8 g/kg diet). The time-dependent effect of eritadenine supplementation was also investigated. Eritadenine supplementation (50 mg/kg diet) significantly decreased the phosphatidylcholine (PC):phosphatidylethanolamine (PE) ratio in liver microsomes and the S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio in the liver, in addition to the plasma cholesterol concentration, irrespective of dietary choline levels. There was a significant correlation between the plasma cholesterol concentration and the liver microsomal PC:PE ratio. Although eritadenine caused fatty liver when added to the diets containing 0 or 2 g/kg choline chloride, a high level (8 g/kg) of choline chloride fully prevented the eritadenine-induced fatty liver without diminution of hypocholesterolemic action. Both the PC:PE ratio and the SAM:SAH ratio decreased significantly prior to the decrease in the plasma cholesterol concentration (1 d vs. 2 d after) in response to eritadenine supplementation, supporting the hypothesis that the alteration of hepatic phospholipid metabolism may be a cause of the hypocholesterolemic action of eritadenine. These observations suggest that the essential hypocholesterolemic action of eritadenine might be associated with a modification of hepatic phospholipid metabolism rather than with the PC deficiency, due to the inhibition of PE N-methylation.
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PMID:Hypocholesterolemic action of eritadenine is mediated by a modification of hepatic phospholipid metabolism in rats. 764 48

Deficiency of choline and methionine produces hepatic steatosis similar to that seen with ethanol, and supplementation with these lipotropes can prevent ethanol-induced fatty liver. These effects are thought to occur through alterations in membrane phospholipid metabolism, but the mechanism whereby this occurs and the precise nature of the changes brought about by ethanol in the interactions of choline and methionine metabolism remain unclear. Through the known effects on hepatic glutathione (which requires as a precursor a product of methionine catabolism), ethanol might affect hepatic one-carbon metabolism, which requires the participation of both methionine and choline in the transfer of methyl groups. This has been investigated with a radiorespirometric technique to assess the in vivo oxidation of the methyl groups of lipotropes and their intermediates in ethnaol- and control-fed rats. Enzyme activities of one-carbon transfer reactions and the hepatic levels of methionine and alpha-aminobutyrate, an end product of methionine catabolism, have been measured. The effect of ethanol feeding on hepatic S-adenosylmethionine and S-adenosylhomocysteine has also been assessed. Ethanol increases the oxidation to carbon dioxide of the methyl group of methionine by a factor of 2.9 (p = 0.002) and produces a 3.6-fold (p = 0.0001) accumulation of alpha-aminobutyrate, indicating a marked increase in methionine catabolism. Hepatic methionine levels are unchanged by ethanol, however, and this may be explained by a dramatic increase in the turnover of the methyl groups of choline and betaine in response to ethanol (times 3.6 and 4.2, respectively, p < 0.003), suggesting greatly increased use of the choline oxidation pathway to remethylate homocysteine through betaine homocysteine methyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of ethanol on one-carbon metabolism: increased methionine catabolism and lipotrope methyl-group wastage. 769 9

The modulation of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) biosynthesis by sulfur-substituted fatty acid analogues has been investigated in rats. We have compared the effects of two non-beta-oxidizable fatty acid analogues, 3-thiadicarboxylic acid and tetradecylthioacetic acid, which induce proliferation of peroxisomes, with those of the analogue tetradecylthiopropionic acid, which is a weak peroxisome proliferator. Repeated administration of 3-thiadicarboxylic acid for seven days resulted in increased hepatic concentrations of both PC and PE, but the PC/PE ratio was decreased. PC synthesis was increased, as evidenced by increased incorporation of [3H]choline into PC and an increased activity of cytidinetriphosphate (CTP): phosphocholine cytidylyltransferase. This was accompanied by a reduction in the pool sizes of choline and phosphocholine. The S-adenosylmethione/S-adenosylhomocysteine ratio (AdoMet/AdoHcy) was marginally affected, indicating no increase in the rate of methylation of PE to PC. Administration of tetradecylthioacetic acid also resulted in increased hepatic phospholipid levels, increased AdoMet/AdoHcy ratios and in slightly elevated activity of CTP:phosphocholine cytidylyltransferase. The most striking effect observed after tetradecylthiopropionic acid treatment was the development of fatty liver. The activity of CTP:phosphocholine cytidylyltransferase and the incorporation of [3H]choline into PC was reduced compared to 3-thiadicarboxylic acid treatment. Although the rate of methylation of PE seemed to be increased at an elevated AdoMet/AdoHcy ratio, this resulted in only minor changes in the hepatic PC and PE levels, and the PC/PE ratio remained unchanged. Furthermore, the hepatic levels of choline and phosphocholine were reduced in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of phosphatidylcholine biosynthesis by peroxisome proliferating fatty acid analogues. 823 55

Previous studies have shown that ethanol feeding to rats alters methionine metabolism by decreasing the activity of methionine synthetase. This is the enzyme that converts homocysteine in the presence of vitamin B12 and N5-methyltetrahydrofolate to methionine. The action of the ethanol results in an increase in the hepatic level of the substrate N5-methyltetrahydrofolate but as an adaptive mechanism, betaine homocysteine methyltransferase, is induced in order to maintain hepatic S-adenosylmethionine at normal levels. Continued ethanol feeding, beyond 2 months, however, produces depressed levels of hepatic S-adenosylmethionine. Because betaine homocysteine methyltransferase is induced in the livers of ethanol-fed rats, this study was conducted to determine what effect the feeding of betaine, a substrate of betaine homocysteine methyltransferase, has on methionine metabolism in control and ethanol-fed animals. Control and ethanol-fed rats were given both betaine-lacking and betaine-containing liquid diets for 4 weeks, and parameters of methionine metabolism were measured. These measurements demonstrated that betaine administration doubled the hepatic levels of S-adenosylmethionine in control animals and increased by 4-fold the levels of hepatic S-adenosylmethionine in the ethanol-fed rats. The ethanol-induced infiltration of triglycerides in the liver was also reduced by the feeding of betaine to the ethanol-fed animals. These results indicate that betaine administration has the capacity to elevate hepatic S-adenosylmethionine and to prevent the ethanol-induced fatty liver.
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PMID:Dietary betaine promotes generation of hepatic S-adenosylmethionine and protects the liver from ethanol-induced fatty infiltration. 833 83

Choline-deficiency causes liver cells to die by apoptosis, and it has not been clear whether the effects of choline-deficiency are mediated by methyl-deficiency or by lack of choline moieties. SV40 immortalized CWSV-1 hepatocytes were cultivated in media that were choline-sufficient, choline-deficient, choline-deficient with methyl-donors (betaine or methionine), or choline-deficient with extra folate/vitamin B12. Choline-deficient CWSV-1 hepatocytes were not methyl-deficient as they had increased intracellular S-adenosylmethionine concentrations (132% of control; P < 0.01). Despite increased phosphatidylcholine synthesis via sequential methylation of phosphatidylethanol-amine, choline-deficient hepatocytes had significantly decreased (P < 0.01) intracellular concentrations of choline (20% of control), phosphocholine (6% of control), glycerophosphocholine (15% of control), and phosphatidylcholine (55% of control). Methyl-supplementation in choline-deficiency enhanced intracellular methyl-group availability, but did not correct choline-deficiency induced abnormalities in either choline metabolite or phospholipid content in hepatocytes. Methyl-supplemented, choline-deficient cells died by apoptosis. In a rat study, 2 weeks of a choline deficient diet supplemented with betaine did not prevent the occurrence of fatty liver and the increased DNA strand breakage induced by choline-deficiency. Though dietary supplementation with betaine restored hepatic betaine concentration and increased hepatic S-adenosylmethionine/S-adenosylhomocysteine ratio, it did not correct depleted choline (15% of control), phosphocholine (6% control), or phosphatidylcholine (48% of control) concentrations in deficient livers. These data show that decreased intracellular choline and/or choline metabolite concentrations, and not methyl deficiency, are associated with apoptotic death of hepatocytes.
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PMID:Methyl-group donors cannot prevent apoptotic death of rat hepatocytes induced by choline-deficiency. 902 80


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