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)

1 A series of experiments were conducted to investigate the effects of dietary retinol status on chickens ingesting aflatoxin B1. The effects of dietary supplementation with biotin and alpha-tocopherol were also examined. 2. Aflatoxin B1 levels greater than 1 mg/kg diet had a detrimental effect on 'liveability', body-weight gain, food intake and food conversion efficiency. When fed for more than 2 weeks aflatoxin increased relative liver weight and liver lipid concentration. These effects were less pronounced with avitaminotic A chickens. 3. A synergistic effect on hydropericardium development was observed between aflatoxin B1 and retinol. This effect was not observed when the dietary level of alpha-tocopherol was increased tenfold. 4. The specific activities of certain hepatic lipogenic and amino acid-metabolizing enzymes were influenced by aflatoxin ingestion. A reduction in lipogenic enzyme activity was observed before a reduction in the activities of amino acid-metabolizing enzymes. 5. Liver fatty acid composition was significantly influenced by aflatoxin B1. The extent of these changes was reduced by the inclusion of additional dietary biotin.
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PMID:The influence of vitamin A status on the response of chickens to aflatoxin B1 and changes in liver lipid metabolism associated with aflatoxicosis. 46 42

Vitamin A is normally transported in plasma as retinol bound to a specific protein, retinol-binding protein (RBP). Detailed studies were conducted to examine the effects of excess vitamin A on the plasma concentration and metabolism of RBP, and to obtain information about vitamin A transport in the hypervitaminotic state. Two separate experiments were conducted. In the first (Study I, 99 days), plasma RBP and vitamin A levels were compared in three groups of rats fed 0.14 mg (control), 7.3 mg (group 2), or 41 mg (group 3) of vitamin A per day. After day 50 of the study, the administration of excess vitamin A to hypervitaminotic rats (groups 2 and 3) was discontinued and the rats were allowed to recover from vitamin A toxicity. In the second, shorter experiment (Study II), serum vitamin A and RBP levels were compared in control and hypervitaminotic (34 mg of retinyl acetate per day) rats. The rats in this study were also given [3-H]retinyl acetate daily to determine the distribution of retinyl esters and retinol between the lipoprotein and nonlipoprotein protein fractions of plasma. In both studies, administration of large, excessive doses of vitamin A resulted in substantial and significant decreases in the levels of serum RBP. Excessive doses of vitamin A produced fatty liver in the rats, in association with a normal (group 2, Study I) or with a decreased (group 3, Study I) level of RBP in the liver. It is possible that excess vitamin A leads to decreased rates of RBP synthesis in, and of RBP secretion from, the liver. Administration of excessive doses of vitamin A also resulted in elevations of serum vitamin A levels, which were mainly due to large increases in the circulating levels of retinyl esters. In the hypervitaminotic rats, most of the serum vitamin A, and virtually all of the retinyl esters, was found in association with the serum lipoproteins of hydrated density less than 1.21. These results demonstrate that the serum lipoproteins play an important role in the transport of the vitamin A that accumulates in serum in hypervitaminosis A. We suggest that the toxic manifestations of hypervitaminosis A occur when vitamin A circulates in plasma and is presented to membranes in a form other than bound to RBP. Plasma lipoproteins may nonspecificially deliver vitamin A to biological membranes and hence lead to vitamin A toxicity.
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PMID:Metabolism of retinol-binding protein and vitamin A during hypervitaminosis A in the rat. 112 57

Liver retinoid levels and the retinyl esters were examined in liver biopsy specimens from 70 patients with alcoholic and nonalcoholic liver diseases. There was a wide variation in the liver retinoid levels. The liver retinoid level was statistically significantly lower in 15 patients with alcoholic liver disease and a depressed Normotest (NT) value of less than 65% compared with patients with alcoholic liver disease and a normal NT value of greater than 65% (P less than 0.01). The mean serum retinol level in patients with alcoholic cirrhosis was 0.68 +/- 0.38 mumol/l compared with 1.99 +/- 1.14 mumol/l in patients with alcoholic fatty liver (P less than 0.03). The relative amount of retinyl oleate was increased in the alcoholic fatty liver compared with the nonalcoholic fatty liver (P less than 0.001).
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PMID:Retinol and retinyl esters in patients with alcoholic liver disease. 292 1

The effects of all-trans and 13-cis retinoic acid upon serum and liver lipids were investigated in Sprague-Dawley rats. Groups of rats were fed daily with 105, 210 and 315 micrograms/g diet of one of the retinoids for periods of up to 8 days. Other groups were injected intraperitoneally (I.P.) daily with retinoids at levels equivalent to the daily intake of rats receiving 105 or 210 micrograms of retinoid/g diet. All dietary concentrations of all-trans retinoic acid induced hypertriglyceridemia, however, only the highest dietary concentration of the 13-cis form caused this response. Injection of the all-trans form consistently increased serum triglycerides, while 13-cis retinoic acid did so in only one case. Retinoid-fed rats fasted for 6 hours before blood sampling demonstrated similar increases in serum triglycerides compared to their respective controls. Also, retinoid administration reduced serum retinol at all levels tested with the all-trans form appearing to be more potent. Growth and feed intake was somewhat reduced in rats receiving the highest level of all-trans retinoic acid. Liver analysis did not reveal fatty liver or alterations in phospholipid, cholesterol, or vitamin A content in any groups monitored. Our previous studies have shown induction of hypertriglyceridemia when rats were fed as low as 26 micrograms/g diet of all-trans retinoic acid. The current studies would indicate that feeding 315 micrograms/g diet of the 13-cis isomer was required to elicit a similar response.
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PMID:Comparative effects of all-trans and 13-cis retinoic acid administration on serum and liver lipids in rats. 735 4

Kwashiorkor remains a significant cause of childhood morbidity and mortality in tropical regions. However, there are relatively few reproducible animal models to elucidate the aetiopathogenesis, biochemical derangements, and morphological changes of this condition. In the present study, 64 weanling male Wistar albino rats were divided into high protein chow, high protein maize starch, and low protein maize starch groups. After 4 weeks on these respective diets, animals on the low protein diet were commenced on the high protein maize starch diet, while those in the other groups were continued on their original diets for a further period of 5 weeks each The low protein group of animals initially showed growth failure, hair loss, oedoma, fatty liver, metabolic acidosis, hypoalbuminaemia, and anaemia, which are characteristic features of human kwashiorkor. These changes were all reversed by dietary rehabilitation with the high protein diet. The reduced plasma retinol, increased plasma alanine and aspartate aminotransferases and fatty liver observed in the low protein group of animals probably suggest an important role for free radicals in the aetiopathogenesis of kwashiorkor.
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PMID:Biochemical changes and liver tissue pathology in weanling Wistar albino rats with protein-energy malnutrition (PEM). 1295 86

Oxidation of ethanol via alcohol dehydrogenase (ADH) explains various metabolic effects of ethanol but does not account for the tolerance. This fact, as well as the discovery of the proliferation of the smooth endoplasmic reticulum (SER) after chronic alcohol consumption, suggested the existence of an additional pathway which was then described by Lieber and DeCarli, namely the microsomal ethanol oxidizing system (MEOS), involving cytochrome P450. The existence of this system was initially challenged but the effect of ethanol on liver microsomes was confirmed by Remmer and his group. After chronic ethanol consumption, the activity of the MEOS increases, with an associated rise in cytochrome P450, especially CYP2E1, most conclusively shown in alcohol dehydrogenase negative deer mice. There is also cross-induction of the metabolism of other drugs, resulting in drug tolerance. Furthermore, the conversion of hepatotoxic agents to toxic metabolites increases, which explains the enhanced susceptibility of alcoholics to the adverse effects of various xenobiotics, including industrial solvents. CYP2E1 also activates some commonly used drugs (such as acetaminophen) to their toxic metabolites, and promotes carcinogenesis. In addition, catabolism of retinol is accelerated resulting in its depletion. Contrasting with the stimulating effects of chronic consumption, acute ethanol intake inhibits the metabolism of other drugs. Moreover, metabolism by CYP2E1 results in a significant release of free radicals which, in turn, diminishes reduced glutathione (GSH) and other defense systems against oxidative stress which plays a major pathogenic role in alcoholic liver disease. CYP1A2 and CYP3A4, two other perivenular P450s, also sustain the metabolism of ethanol, thereby contributing to MEOS activity and possibly liver injury. CYP2E1 has also a physiologic role which comprises gluconeogenesis from ketones, oxidation of fatty acids, and detoxification of xenobiotics other than ethanol. Excess of these physiological substrates (such as seen in obesity and diabetes) also leads to CYP2E1 induction and nonalcoholic fatty liver disease (NAFLD), which includes nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), with pathological lesions similar to those observed in alcoholic steatohepatitis. Increases of CYP2E1 and its mRNA prevail in the perivenular zone, the area of maximal liver damage. CYP2E1 up-regulation was also demonstrated in obese patients as well as in rat models of obesity and NASH. Furthermore, NASH is increasingly recognized as a precursor to more severe liver disease, sometimes evolving into "cryptogenic" cirrhosis. The prevalence of NAFLD averages 20% and that of NASH 2% to 3% in the general population, making these conditions the most common liver diseases in the United States. Considering the pathogenic role that up-regulation of CYP2E1 also plays in alcoholic liver disease (vide supra), it is apparent that a major therapeutic challenge is now to find a way to control this toxic process. CYP2E1 inhibitors oppose alcohol-induced liver damage, but heretofore available compounds are too toxic for clinical use. Recently, however, polyenylphosphatidylcholine (PPC), an innocuous mixture of polyunsaturated phosphatidylcholines extracted from soybeans (and its active component dilinoleoylphosphatidylcholine), were discovered to decrease CYP2E1 activity. PPC also opposes hepatic oxidative stress and fibrosis. It is now being tested clinically.
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PMID:The discovery of the microsomal ethanol oxidizing system and its physiologic and pathologic role. 1555 33

Liver fatty acid metabolism of male rats fed on a vitamin A-deficient diet for 3 months from 21 d of age was evaluated. Vitamin A restriction produced subclinical plasma and negligible liver retinol concentrations, compared with the control group receiving the same diet with 4000 IU vitamin A (8 mg retinol as retinyl palmitate)/kg diet. Vitamin A deficiency induced a hypolipidaemic effect by decreasing serum triacylglycerol, cholesterol and HDL-cholesterol levels. The decrease of liver total phospholipid was associated with low phosphatidylcholine synthesis observed by lower [14C]choline incorporation into phosphatidylcholine, compared with control. Also, liver fatty acid synthesis decreased, as was indicated by activity and mRNA expression of acetyl-CoA carboxylase (ACC), and incorporation of [14C]acetate into saponified lipids. A decrease of the PPARalpha mRNA expression was observed. Liver mitochondria of vitamin A-deficient rats showed a lower total phospholipid concentration coinciding with a decrease of the cardiolipin proportion, without changes in the other phospholipid fractions determined. The mitochondria fatty acid oxidation increased by 30 % of the control value and it was attributed to a high activity and mRNA expression of carnitine palmitoyltransferase-I (CPT-I). An increase in serum beta-hydroxybutyrate levels was observed in vitamin A-deficient rats. Vitamin A deficiency alters the mitochondria lipid composition and also enhances fatty acid oxidation by modifying the production of malonyl-CoA, the endogenous inhibitor of CPT-I, due to decreased activity of liver ACC. The incorporation of vitamin A into the diet of vitamin A-deficient rats reverted all the changes observed.
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PMID:Vitamin A deficiency modifies lipid metabolism in rat liver. 1729 94

The objective of the present study was to identify the factors which contribute to the appearance and/or aggravation of Vitamin A Deficiency (VAD) in individuals with morbid obesity in the pre- and postoperative stages of Roux-en-Y gastric bypass (RYGBP). Bibliography searches were done in the data-bases of Medline and Lilacs, published in the last 35 years, priorizing the studies which assessed VAD through serum levels of retinol. The principal factors identified as contributors to VAD were oxidative stress, deficiency of other nutrients, lipid malabsorption in the postoperative stage, insufficient intake of lipids and food sources of Vitamin A, and presence of nonalcoholic fatty liver disease. The investigation of the nutritional status of Vitamin A in those individuals may foment intervention strategies easily incorporated in already established routine procedures, aiming to reduce VAD rates, which will reflect upon those individuals' quality of life.
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PMID:Nutritional status of vitamin A in morbid obesity before and after Roux-en-Y gastric bypass. 1789 59

Retinol binding protein 4 (RBP4) is a protein secreted by adipocytes, and closely associated with insulin resistance. Whereas RBP4 is also mainly expressed in hepatocytes as the principal transport protein for retinol (vitamin A) in the circulation, and its pathophysiological role in liver remain unclear. The aim of this paper was to investigate the association between RBP4 and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Serum RBP4 and adiponectin concentrations were measured by radioimmunoassay in 52 diabetic patients who had NAFLD and 50 sex- and age-matched diabetic patients without any clinical features of liver diseases who had normal liver ultrasonic appearance and normal liver function. Serum RBP4 levels were elevated in diabetic patients with NAFLD (32.0+/-8.9 microg/ml vs. 41.3+/-9.8 microg/ml, p<0.001), while adiponectin decreased (17.4+/-9.3 microg/ml vs. 13.8+/-7.0 microg/ml, p=0.032). Male diabetic patients had higher serum RBP4 concentration and lower serum adiponectin concentration than female diabetic patients (38.5+/-9.9 microg/ml vs. 34.0+/-10.7 microg/ml, p=0.031 and 12.7+/-5.7 microg/ml vs. 20.23+/-9.8 microg/ml, p<0.001, respectively). Multiple logistic regression analysis revealed RBP4 and triglyceride as independent association factors for NAFLD, while the association between serum adiponectin and NAFLD was not significant. Increasing concentrations of RBP4 were independently and significantly associated with NAFLD in diabetic patients. In multiple linear regression analysis, alanine aminotransferase, fasting serum insulin and adiponectin were independent factors for serum RBP4 level. The study demonstrates that retinol binding protein 4 might contribute to the pathogenesis of nonalcoholic fatty liver disease.
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PMID:Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. 1790 83

Cellular retinol-binding protein (CRBP) type III (CRBP-III) belongs to the family of intracellular lipid-binding proteins, which includes the adipocyte-binding protein aP2. In the cytosol, CRBP-III binds retinol, the precursor of retinyl ester and the active metabolite retinoic acid. The goal of the present work is to understand the regulation of CRBP-III expression and its role in lipid metabolism. Using EMSAs, luciferase reporter assays, and chromatin immunoprecipitation assays, we found that CRBP-III is a direct target of peroxisome proliferator-activated receptor-gamma (PPARgamma). Moreover, CRBP-III expression was induced in adipose tissue of mice after treatment with the PPARgamma agonist rosiglitazone. To examine a potential role of CRBP-III in regulating lipid metabolism in vivo, CRBP-III-deficient (C-III-KO) mice were maintained on a high-fat diet (HFD). Hepatic steatosis was decreased in HFD-fed C-III-KO compared with HFD-fed wild-type mice. These differences were partly explained by decreased serum free fatty acid levels and decreased free fatty acid efflux from adipose tissue of C-III-KO mice. In addition, the lack of CRBP-III was associated with reduced food intake, increased respiratory energy ratio, and altered body composition, with decreased adiposity and increased lean body mass. Furthermore, expression of genes involved in mitochondrial fatty acid oxidation in brown adipose tissue was increased in C-III-KO mice, and C-III-KO mice were more cold tolerant than wild-type mice fed an HFD. In summary, we demonstrate that CRBP-III is a PPARgamma target gene and plays a role in lipid and whole body energy metabolism.
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PMID:Cellular retinol-binding protein type III is a PPARgamma target gene and plays a role in lipid metabolism. 1884 Jul 64


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