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 purpose of this study was to observe the effects of hepatic impairment on the metabolism of fructose and 5-fluorouracil (5-FU) in fatty liver models using in vivo 31P-MRS and 19F-MRS and to compare the results. In addition, we compared the results to those of other conventional tests such as laboratory examinations, imaging and pathology. Male SIc:Wistar rats were examined on BEM170/200 (4.7 T, Otsuka Electronics, USA) with 17-mm diameter surface coil. Fatty liver was induced by a choline deficient diet (CD diet) for 2 weeks. 31P-MRS were obtained for 90 min after intravenous (i.v.) injection of 1 g/kg of fructose and 19F-MRS were measured for 100 min after i.v. injection of 100 mg/kg of 5-FU. 1H-MRS and 1H-MRI were also performed. On 31P-MRS, there was no statistical difference in the time course of phosphomonoester (PME), adenosine triphosphate (ATP), and inorganic phosphate (Pi) between CD diet group and control group. On 19F-MRS, we detected high peak of fluoronucleotide (Fnct) and suppressed peak of alpha-fluoro-beta-alanine (FBAL) in CD diet group. We showed the metabolism of fructose and 5-FU by 31P-MRS and 19F-MRS, respectively. There was no difference in fructose metabolism but we observed increased fluoronucleotide and decreased a-fluoro-b-alanine in 5-FU metabolism of fatty liver. We speculate that the effects of hepatic impairment in fatty liver may be more severe on 5-FU metabolism and the increased fluoronucleotide may reflect cell proliferation.
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PMID:Effects of hepatic impairment on the metabolism of fructose and 5-fluorouracil, as studied in fatty liver models using in vivo 31P-MRS and 19F-MRS. 1021 84

Alcohol was administered chronically to female Sprague-Dawley rats in a nutritionally adequate totally liquid diet for 28 days. This resulted in significant hepatic steatosis and lipid peroxidation. Beta-alanine, when co-administered with alcohol, seemed to increase hepatic steatosis, as assessed histologically, but decreased triglyceride levels as measured biochemically. In addition, beta-alanine and especially alcohol co-administered with beta-alanine, significantly increased homocysteine and cysteine excretion into urine throughout the 28-day period of ethanol administration. Serum homocysteine levels were significantly higher in alcohol- and alcohol plus beta-alanine-treated animals compared to pair-fed control animals. Alcohol did not affect the urinary excretion of taurine, except after 21 days, when levels were reduced. Levels of liver taurine were markedly depleted in animals receiving alcohol and particularly alcohol plus beta-alanine, compared to pair-fed controls. Liver and serum taurine levels were also markedly depleted in animals receiving beta-alanine and alcohol plus beta-alanine, compared to non-beta-alanine-treated animals. There was evidence of slight cholestasis in animals treated with alcohol and more so with alcohol plus beta-alanine, as indicated by raised serum alkaline phosphatase and bile acids. These in vivo findings demonstrate for the first time that animals treated with beta-alanine may be more susceptible to ethanol-induced hepatic dysfunction, possibly as a result of taurine depletion.
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PMID:The effect of taurine depletion by beta-alanine treatment on the susceptibility to ethanol-induced hepatic dysfunction in rats. 1113 13

The effects of a moderately energy-restricted (25 kcal/kg) diet on liver-function tests, anthropometric measurements, mononuclear-cell phospholipid fatty acid, lymphocyte blastogenesis, and plasma prostaglandin E2 and alpha-tocopherol levels were observed at weeks 0, 8, and 24 in 14 obese patients with fatty liver. Serum aminotransferase levels were improved significantly, with decreases in the body mass index and waist circumference. Decreases in energy intake from carbohydrate and increases in intake of vitamin A, vitamin C, and vegetables were observed at week 24. In mononuclear-cell phospholipids, linoleic acid (18:2omega 6), which was significantly lower in patients than in controls at week 0, was increased at week 24. In contrast, arachidonic acid was decreased. Plasma prostaglandin E2 levels were significantly lower in patients than in controls at week 0 and increased at week 24. The mononuclear-cell response for phytohemagglutinin correlated with 18:2omega 6 in mononuclear-cell phospholipids (r = 0.692, P < 0.01). Improvement of the serum alanine-aminotransferase level correlated with an increase in the plasma alpha-tocopherol level (r = -0.667, P < 0.01) and increases in consumption of vitamin A, omega 3 polyunsaturated fatty acids, and vegetables. These findings suggest that a hypoenergetic diet rich in omega 3 polyunsaturated fatty acids and antioxidants might be beneficial for obese patients with fatty liver.
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PMID:Effect of a moderately energy-restricted diet on obese patients with fatty liver. 1144 71

Nonalcoholic fatty liver disease, an entity that includes nonalcoholic steatohepatitis, is typically a benign, indolent condition. However, in a subset of patients, the clinical course may progress to advanced cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Unfortunately, the pathogenesis, natural history, and potential therapies for these disorders remain poorly understood. Identifying patients who should be targeted for potential treatment remains difficult. Liver biopsy should be considered to assess the degree of hepatic inflammation and fibrosis, because physical examination findings, biochemical parameters, and the results of radiographic studies have been shown to correlate poorly with the severity of steatohepatitis and fibrosis. Although there is some evidence suggesting that obesity, diabetes mellitus, older age, and perhaps an aspartate transaminase:alanine aminotransaminase ratio higher than 1 may be predictors of more advanced fibrosis, histology remains the gold standard. Most patients with simple hepatic steatosis appear to follow a benign course and probably do not require aggressive therapy. Conversely, patients with steatohepatitis with extensive inflammation and fibrosis are the patients who are most likely to benefit from effective therapies. The most commonly recommended treatment is weight loss. Existing data suggest that rapid weight loss may promote hepatic inflammation and fibrosis; therefore, gradual weight loss should be recommended. Large, randomized, controlled trials evaluating the long-term histologic impact and clinical outcomes of weight loss strategies are lacking. Potentially promising pharmacologic therapies include insulin-sensitizing oral hypoglycemic agents such as metformin and the thiazolidenediols, antihyperlipidemic agents such as gemfibrozil or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, vitamin E and other antioxidants, ursodeoxycholic acid, and betaine. As with weight loss, data regarding the efficacy of these pharmacologic options are limited. In addition, there are no widely accepted guidelines to help direct the clinician in the optimal use of these agents in patients with nonalcoholic fatty liver diseases.
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PMID:Therapeutic Options in Nonalcoholic Fatty Liver Disease. 1240 79

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

To investigate the associations between obesity and serum hepatic enzyme activities, we measured total body fat (TBF), body mass index (BMI), and hepatic biochemical parameters in 732 apparently healthy adults. TBF was assessed using a body fat analyzer. Serum activities of alanine and aspartate aminotransferase (ALT and AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LD) were determined by standard spectrophotometric methods. Mean activities (+/- SD) of serum ALT and AST in men with high fatness were 51.2 +/- 12.6 U/L and 32.9 +/- 9.2 U/L, which were significantly higher than those in men with low fatness (23.5 +/- 7.4 U/L and 22.5 +/- 7.8 U/L, p < 0.01). Of 147 men with high fatness, 56 (38.1%) had serum ALT levels above the upper limit of normal, whereas only 9.5% (31/328) of men with low or desirable fatness showed elevated serum ALT activities (p < 0.01). Serum ALT, AST, and GGT activities correlated significantly with TBF in both overweight men and women. Among subjects having high TBF, those with fatty liver showed significantly higher incidence of elevated hepatic enzymes, compared to those without fatty liver. In short, elevated serum hepatic enzyme activities are associated with TBF and a high prevalence of fatty liver is observed in subjects with elevated TBF.
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PMID:Association between elevated serum hepatic enzyme activity and total body fat in obese humans. 1295 39

Alanine aminotransferase (ALT) is a widely used index of liver integrity or hepatocellular damage in clinics as well as a key enzyme in intermediatary metabolism. In this study, we have cloned the complementary DNAs of murine homologues of human alanine aminotransferase 1 and 2 (ALT1 and ALT2). The deduced peptides of murine ALT1 (mALT1) and ALT2 (mALT2) share 87% and 93% identity, respectively, with their human counterparts at the amino acid level. Murine ALT genes localize to separate chromosomes, with mALT1 gene (gpt1) on chromosome 15 and mALT2 gene (gpt2) on chromosome 8. The murine gpt1 and gpt2 differ in messenger RNA expression: gpt1 is mainly expressed in liver, bowel, and white adipose tissue and gpt2 is highly expressed in muscle, liver, and white adipose tissue. Expression of recombinant mALT1 and mALT2 proteins in Escherichia coli (E. coli) produced functional enzymes that catalyze alanine transamination. The potential diagnostic value of ALT isoenzymes in liver disease was evaluated in an obese animal model. In fatty livers of obese mice, ALT2 gene expression is induced 2-fold, but ALT1 remains the same. Furthermore, in fatty liver, total hepatic ALT activity is elevated significantly by 30% whereas aspartate aminotransferase (AST) activity remains unchanged. In conclusion, these results indicate that ALT2 may be responsible for the increased ALT activity in hepatic steatosis and provide evidence that an ALT isoenzyme-specific assay may have more diagnostic value than the total ALT activity assay currently in clinical use.
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PMID:Murine alanine aminotransferase: cDNA cloning, functional expression, and differential gene regulation in mouse fatty liver. 1512 58

Liver disease is characterized by fatty liver, hepatitis, fibrosis and cirrhosis and is a major cause of illness and death worldwide. The prevalence of liver diseases highlights the need for animal models for research on the mechanism of disease pathogenesis and efficient and cost-effective treatments. Here we show that a senescence-accelerated mouse strain (SAMP8 mice), displays severe liver pathology, which is not seen in senescence-resistant mice (SAMR1). The livers of SAMP8 mice show fatty degeneration, hepatocyte death, fibrosis, cirrhotic changes, inflammatory mononuclear cell infiltration and sporadic neoplastic changes. SAMP8 mice also show abnormal liver function tests: significantly increased levels of alanine amino-transferase (ALT) and aspartate aminotransferase (AST). Furthermore, titers of murine leukemia virus are higher in livers of SAMP8 than in those of SAMR1 mice. Our observations suggest that SAMP8 mouse strain is a valuable animal model for the study of liver diseases. The possible mechanisms of liver damage in SAMP8 mice are also discussed.
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PMID:Pathological changes in the liver of a senescence accelerated mouse strain (SAMP8): a mouse model for the study of liver diseases. 1537 57

The aim of this study was to evaluate the correlation of ultrasonography-proven fatty liver with liver functions, serum lipid levels and anthropometric measurements in children with exogenous obesity. Three hundred and twenty-two patients (183 girls, 56.8%) with a mean age of 11.4+/-3.2 years (4-18 years) who presented with the complaint of obesity were enrolled. In 38 (11.8%) patients, increased liver echogenicity resembling fatty liver was found (Group 1). The body mass index percentages of group 1 patients were significantly higher than of those without fatty liver (Group 2) (157.7+/-18.0 vs 151.3+/-17.8, p=0.038). Alanine and aspartate aminotransferase levels of group 1 patients were significantly higher than of group 2 (p=0.002 vs p=0.028, respectively). Triglyceride levels were significantly higher in group 1 patients (120.8+/-88.8 vs 100.5+/-58.5 mg/dl, p=0.044). In conclusion, ultrasonography is an easy and noninvasive method for the diagnosis of fatty liver in children with obesity. Body mass index and serum lipids were higher in group 1 patients. The diagnosis and early treatment of obesity in childhood is important for the prevention and better treatment of related complications. Thus, ultrasonography should be a part of the early evaluation of obese children.
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PMID:Fatty liver in obese children: prevalence and correlation with anthropometric measurements and hyperlipidemia. 1588 25

Fatty liver at ultrasounds, with/ without raised plasma levels of hepatic enzymes, is common in obesity. In most cases, it is the hallmark of non-alcoholic fatty liver disease (NAFLD), a potentially progressive disease associated with insulin resistance and the metabolic syndrome (MS). We tested the hypothesis that insulin resistance per se might be associated with hepatocellular necrosis. Alanine and aspartate aminotransferases (ALT and AST; no.=799) and gamma-glutamyltranspeptidase (GGT; no.=459) were analyzed in a group of treatment-seeking obese patients recruited in 12 Italian medical centers. Insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR; no.=522). Median ALT and AST increased with increasing obesity class (p=0.001 and p=0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased with the obesity class (p<0.0001), and was higher in subjects with elevated ALT (median, 4.93 vs 2.89; p<0.0001). A significant correlation was observed between HOMA-IR and ALT (R2=0.208; p<0.0001), as well as between HOMA-IR and AST or GGT (R2=0.112 and R2=0.080; p<0.0001). The correlation was maintained when cases with elevated enzyme levels were omitted from analysis. Diabetes and hypertriglyceridemia were the features of the MS most commonly associated with raised liver enzymes. In logistic regression, after correction for age, gender, BMI and features of the MS, HOMA-IR maintained a highly predictive value for raised ALT, AST and GGT. We conclude that in obesity insulin resistance is a risk factor for raised liver enzyme levels, possibly related to NAFLD.
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PMID:Aminotransferase and gamma-glutamyltranspeptidase levels in obesity are associated with insulin resistance and the metabolic syndrome. 1596 6


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