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)

The fatty liver and hypolipidemia caused by aflatoxin B1 (AFB1) were studied in male Sprague-Dawley rats fed Purina Rat Chow with or without L-carnitine supplement for 6 weeks. In Experiment 1, the rats (n = 20) were divided into four groups, i.e., nonsupplemented control (NSC), nonsupplemented AFB1 (NSA), carnitine supplemented control (CSC), and carnitine supplemented AFB1 (CSA). The NSA and CSA groups were given an oral dose of [3H]AFB1 (1 mg/kg) 6 hr before kill. In Experiment 2 (n = 10) there were only NSA and CSA groups and they were killed 24 hr post-AFB1 administration. Hepatic and plasma concentrations of total lipid, triglycerides, AFB1-macromolecules adducts and urinary excretion of AFB1 were determined. Carnitine supplementation ameliorated AFB1-induced hepatic steatosis and hypolipidemia. Supplementary carnitine reduced covalent binding of AFB1 to hepatic DNA, RNA, and protein. The carnitine effect was more pronounced after 24 hr than after 6 hr of AFB1 treatment. We conclude that supplementary carnitine suppressed AFB1-induced fatty liver and AFB1-macromolecule adduct formation in the rat.
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PMID:Suppression of aflatoxin B1-induced lipid abnormalities and macromolecule-adduct formation by L-carnitine. 138 May 53

Previous studies in our laboratories have revealed that juvenile visceral steatosis mice show suppressed transcription of urea cycle enzyme genes during development and are systemically deficient in carnitine. It has not yet been explained, however, how this carnitine deficiency relates to the abnormal gene expression. We investigated the effect of carnitine on abnormal gene expression, growth retardation, and fatty liver. Carnitine administration relieved the suppression of the developmental induction of two urea cycle enzymes examined, carbamoyl-phosphate synthetase and argininosuccinate synthase, and kept the activities of enzymes normal. However, carnitine did not reduce accumulated lipid in the liver to the normal level. These results suggest that carnitine deficiency plays an important role in the abnormal expression of urea cycle enzyme genes and that the abnormal expression of the genes is not directly caused by lipid accumulation in the liver.
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PMID:Carnitine administration to juvenile visceral steatosis mice corrects the suppressed expression of urea cycle enzymes by normalizing their transcription. 154 87

We analyzed carnitine profiles in C3H-H-2 degrees strain of mouse associated with fatty liver, hyperammonemia and hypoglycemia (Koizumi et al., 1988). Carnitine levels in serum, liver and muscle of mouse with fatty liver were markedly decreased in comparison with those of control mouse (littermates without fatty liver). This is a useful animal model to analyze the role of carnitine in lipid, amino acid and carbohydrate metabolism.
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PMID:Animal model of systemic carnitine deficiency: analysis in C3H-H-2 degrees strain of mouse associated with juvenile visceral steatosis. 199 78

Rats treated with six to eight doses (80 mg/kg, i.p.) of 4-pentenoic acid, an inhibitor of mitochondrial fatty acid oxidation in vitro, during a 48-hr starvation period developed microvesicular fatty infiltration of the liver similar to that observed in Reye's Syndrome. Hepatic triglycerides were elevated an average of 5-fold, although considerable variability was found between individual rats. Fed rats did not develop fatty liver upon similar treatment with pentenoic acid. Liver mitochondria isolated from rats with pentenoic acid-induced fatty liver showed a persistent inhibition of fatty acid oxidation. Rates of oxidation of palmitoylcarnitine and decanoylcarnitine were decreased about 70%, while that of octanoylcarnitine was decreased 50%. Carnitine-independent oxidation of octanoate was also inhibited. Oxidation rates for substrates other than fatty acids, including glutamate, succinate, pyruvate, and alpha-ketoglutarate, were unaffected. Measurements of flavoprotein reduction in intact mitochondria indicated that neither palmitoylcarnitine nor palmitoyl CoA plus L-carnitine could elicit reduction of acyl-CoA dehydrogenase and electron transferring flavoprotein in mitochondria from rats with pentenoic acid-induced fatty liver. These results support a site of inhibition of mitochondrial beta-oxidation at the level of acyl-CoA dehydrogenase for pentenoic acid treatment in vivo, and they suggest a role for nutritional or hormonal factors in the metabolic disposition of pentenoic acid in vivo and in the development of fatty liver.
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PMID:Inhibition of mitochondrial fatty acid oxidation in pentenoic acid-induced fatty liver. A possible model for Reye's syndrome. 671 30

Carnitine-mediated prevention of ethanol-induced hepatic steatosis is related to the attenuation of ethanol metabolism by carnitine in the intact rat. Although carnitine retards ethanol oxidation in the intact animal, the in vitro activities of ethanol-metabolizing enzymes remain unaltered. Therefore, hepatocytes were targeted to understand the mechanism of carnitine effect on ethanol metabolism. Rat hepatocytes were isolated by a collagenase-perfusion technique and incubated in albumin-containing medium with ethanol in the presence or absence of added carnitine or related compounds. Ethanol oxidation was determined by the loss of ethanol as well as by the products formed. The rate of ethanol oxidation in the presence of carnitine was one-half the rate in the absence of carnitine (14 vs. 25 nmol.min-1.million-1 cells). It took 100 times the concentration of carnitine to equal the maximal inhibition produced by acetylcarnitine and the effect of acetylcarnitine was without a lag time. It is concluded that acetylcarnitine is the mediator of carnitine inhibition of ethanol oxidation.
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PMID:Acetylcarnitine-mediated inhibition of ethanol oxidation in hepatocytes. 763 64

In experimental animals the enhancement of hepatic fatty acid oxidation and ketogenic capacity is accompanied by a rise in the concentration of liver carnitine. Massive obesity is characterized by enhanced fatty acid turnover, insulin resistance, and often a fatty liver. Carnitine concentrations were determined in liver, abdominal muscle tissue, and blood in morbidly obese women. The liver and muscle carnitine concentrations were significantly higher in the obese subjects than in the lean control subjects. These findings suggest an increase of the whole-body carnitine pool. In the obese subjects there was also a significant positive correlation between liver and muscle carnitine concentrations. In the majority of the obese subjects fatty changes could be demonstrated in the liver. The plasma insulin concentration tended to be positively correlated with the degree of fat infiltration and negatively correlated with the liver carnitine content. It is concluded that the liver carnitine content is significantly increased in obese women, which agrees with the finding in experimental animals.
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PMID:Increased liver carnitine content in obese women. 782 32

AIM:To investigate the effects of carnitine on ameliorating hepatic steatosis induced by total parenteral nutrition (TPN) in animal model.METHODS: Eighteen normal Wistar rats and 19 cirrhotic Wistar rats induced by carbon tetrachloride were randomly divided into three groups, i.e., free access to food and drink (group A), TPN (group B) and TPN+carnitine (group C) for one week, respectively. Hepatic function, histology and its fat content were determined on the 7th day.RESULTS: Hepatic triglyceride (TG) and cholesterol (CHO) contents were significantly higher in groups B and C than in group A,and significantly lower in group C than in group B in both normal and cirrhotic rats (all P < 0.05). Histopathological examinations revealed that hepatic steatosis was more severe in group B than in group C in both normal and cirrhotic rats.CONCLUSION:Carnitine can ameliorate hepatic steatosis associated with TPN in both non-cirrhotic and cirrhotic rats.
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PMID:A study of the ameliorating effects of carnitine on hepatic steatosis induced by total parenteral nutrition in rats. 1181 55

We describe a 21-year-old male with previously normal plasma total and free carnitine levels who developed a deficiency manifest by decreased plasma and muscle total and free carnitine, decreased urine carnitine, severe hepatic steatosis, mediastinal lipomatosis, progressively impaired triglyceride clearance, myopathy and intermittent hypoglycemia. This case demonstrates that systemic carnitine deficiency may occur in some patients receiving long term carnitine-free TPN. Carnitine may be an essential element of the diet in this patient population.
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PMID:Late onset primary systemic carnitine deficiency exacerbated by carnitine-free parenteral nutrition. 1684 23

Insulin sensitizers like metformin generally act through pathways triggered by adenosine monophosphate-activated protein kinase. Carnitine palmitoyltransferase 1 (CPT1) controls mitochondrial beta-oxidation and is inhibited by malonyl-CoA, the product of acetyl-CoA carboxylase (ACC). The adenosine monophosphate-activated protein kinase-ACC-CPT1 axis tightly regulates mitochondrial long-chain fatty acid oxidation. Evidence indicates that ACC2, the isoform located in close proximity to CPT1, is the major regulator of CPT1 activity. ACC2 as well as CPT1 are therefore potential targets to treat components of the metabolic syndrome such as obesity and insulin resistance. Reversible inhibitors of the liver isoform of CPT1, developed to prevent ketoacidosis and hyperglycemia, have been found to be associated with side effects like hepatic steatosis. However, stimulation of systemic CPT1 activity may be an attractive means to accelerate peripheral fatty acid oxidation and hence improve insulin sensitivity. Stimulation of CPT1 can be achieved by elimination or inhibition of ACC2 activity and through activating transcription factors like peroxisome proliferator-activated receptors and their protein partners. The latter leads to enhanced CPT1 gene expression. Recent developments are discussed, including a recently identified CPT1 isoform, i.e. CPT1C. This protein is highly expressed in the brain and may provide a target for new tools to prevent obesity.
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PMID:Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome. 1969 67

BACKGROUND: Abnormal fatty acid metabolism is an important feature in the mechanisms of insulin resistance and beta-cell dysfunction. Carnitine palmitoyltransferase-1a (CPT-1a, liver isoform) plays a pivotal role in the regulation of mitochondrial fatty acid oxidation. We investigated the role of CPT-1a in the development of impaired glucose tolerance using a mouse model for CPT-1a deficiency when challenged by either a high-carbohydrate (HCD) or a high-fat diet (HFD) for a total duration of up to 46 weeks. METHODS: Insulin sensitivity and glucose tolerance were assessed in heterozygous CPT-1a deficient (CPT-1a+/-) male mice after being fed either a HCD or a HFD for durations of 28 weeks and 46 weeks. Both glucose and insulin tolerance tests were used to investigate beta-cell function and insulin sensitivity. Differences in islet insulin content and hepatic steatosis were evaluated by morphological analysis. RESULTS: CPT-1a+/- mice were more insulin sensitive than CPT-1a+/+ mice when fed either HCD or HFD. The increased insulin sensitivity was associated with an increased expression of Cpt-1b (muscle isoform) in liver, as well as increased microvesicular hepatic steatosis compared to CPT-1a+/+ mice. CPT-1a+/- mice were more glucose tolerant than CPT-1a+/+ mice when fed the HCD, but there was no significant difference when fed HFD. Moreover, CPT-1a+/- mice fed HFD or HCD had fewer and smaller pancreatic islets than CPT-1a+/+ mice. CONCLUSIONS: CPT-1a deficiency preserved insulin sensitivity when challenged by long term feeding of either diet. Furthermore, CPT-1a deficient mice had distinct phenotypes dependent on the diet fed demonstrating that both diet and genetics collectively play a role in the development of impaired glucose tolerance.
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PMID:Long term effects of high fat or high carbohydrate diets on glucose tolerance in mice with heterozygous carnitine palmitoyltransferase-1a (CPT-1a) deficiency: Diet influences on CPT1a deficient mice. 2222 81


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