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)

Transplantation of a fatty liver is associated with a higher incidence of primary non-function of the graft. Indocyanine green (ICG) has been used for assessing hepatic dysfunction but not for quantifying liver steatosis. New Zealand white rabbits were fed a normal diet (group A) or a high-cholesterol (2%) diet for 4, 8, and 12 weeks in groups B, C, and D, respectively. Laparotomy was performed for liver exposure. Hepatic artery, portal vein, and total blood flow, hepatic microcirculation, portal pressure, liver function parameters, and blood cholesterol levels were measured. The hepatic ICG concentration was measured using near-infrared spectroscopy, and its uptake and excretion rates were calculated. The severity of steatosis was assessed from liver biopsy specimens by a semiquantitative grading system. Cholesterol feeding resulted in mild steatosis after 4 weeks and in moderate steatosis after 8 and 12 weeks. Mild steatosis was associated with insignificant changes in haemodynamic parameters, liver function, and ICG handling as compared with controls. Moderate steatosis caused a significant reduction in portal and total hepatic blood flow and microcirculation with a significant increase in hepatic artery flow and portal pressure. These haemodynamic changes were associated with a significant alteration in liver function tests. With moderate steatosis, ICG uptake and excretion were significantly reduced. The ICG uptake rate significantly correlated with total blood flow and microcirculation. The ICG excretion rate significantly correlated with the changes in bilirubin, liver enzymes, and albumin. Direct ICG quantification by near-infrared spectroscopy could be used to assess the severity of hepatic steatosis by reflecting impaired parenchymal perfusion and liver dysfunction.
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PMID:Hepatic indocyanine green uptake and excretion in a rabbit model of steatosis. 1149 Jan 22

Increasing evidence indicates the involvement of immune reactions in the pathogenesis of alcoholic liver disease. We have investigated whether ethanol-induced oxidative stress might contribute to immune response in alcoholics. Antibodies against human serum albumin modified by reaction with malondialdehyde (MDA), 4-hydroxynonenal (HNE), 2-hexenal, acrolein, methylglyoxal, and oxidized arachidonic and linoleic acids were measured by ELISA in 78 patients with alcoholic cirrhosis and/or hepatitis, 50 patients with nonalcoholic cirrhosis, 23 heavy drinkers with fatty liver, and 80 controls. Titers of IgG-recognizing epitopes derived from MDA, HNE, and oxidized fatty acids were significantly higher in alcoholic as compared to nonalcoholic cirrhotics or healthy controls. No differences were instead observed in the titers of IgG-recognizing acrolein-, 2-hexenal-, and methylglyoxal-modified albumin. Alcoholics showing high IgG titers to one adduct tended to have high titers to all the others. However, competition experiments showed that the antigens recognized were structurally unrelated. Anti-MDA and anti-HNE antibodies were significantly higher in cirrhotics with more severe disease as well as in heavy drinkers with cirrhosis or extensive fibrosis than in those with fatty liver only. We conclude that antigens derived from lipid peroxidation contribute to the development of immune responses associated with alcoholic liver disease.
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PMID:Lipid peroxidation contributes to immune reactions associated with alcoholic liver disease. 1175 15

The pathophysiology of hepatic steatosis, a prerequisite of nonalcoholic fatty liver disease, is poorly understood. Because very-low-density lipoprotein (VLDL) formation is the chief route of hepatic lipid export, we hypothesized that the synthesis of apoB-100, a rate-determining step in hepatic VLDL formation, may be altered in patients with nonalcoholic steatohepatitis (NASH). This study evaluated the relative synthesis rates of apolipoprotein B-100 (apoB-100) in patients with NASH and in lean and body mass index (BMI)-matched (obese) controls without NASH. A primed continuous infusion of L-[1-(13)C] leucine was used to measure the absolute synthesis rates (ASR) of apoB-100 and fibrinogen in 7 patients with NASH and compared them with 7 lean and 7 obese (BMI-matched) controls without NASH. The ASRs of fibrinogen and albumin also were measured. The mean ASR of apoB-100 in patients with NASH was lower (31.5 +/- 3.4 mg/kg/d) than that of obese (115.2 +/- 7.2 mg/kg/d, P <.001) and lean controls (82.4 +/- 4.1 mg/kg/d, P =.002). In contrast, the mean ASR of fibrinogen was greater in subjects with NASH than in both control groups. These data indicate that NASH is associated with markedly altered hepatic synthesis of apoB-100. The finding that albumin synthesis was not similarly decreased in patients with NASH shows that the attenuation of apoB-100 synthesis is not on the basis of globally impaired hepatic protein synthesis. In conclusion, because apoB-100 synthesis is a rate-determining step in hepatocyte lipid export, decreased synthesis of this protein may be an important factor in the development of hepatic steatosis, a prerequisite for NASH.
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PMID:Apolipoprotein synthesis in nonalcoholic steatohepatitis. 1214 70

When confronted with liver abnormalities during the third trimester of pregnancy, one should consider acute fatty liver of pregnancy. The differential diagnosis with (pre-)eclampsia and HELLP syndrome is sometimes difficult. In these cases a liver biopsy is helpful though rarely performed during pregnancy. After delivery of the child the liver test abnormalities will ultimately disappear. Recent publications reveal that a dysfunction in the beta-oxidation of mitochondrial fatty acids may contribute to the aetiology of this rare disorder. We describe a case of acute fatty liver in pregnancy, with liver dysfunction (decreased albumin, prolonged prothrombin time) slowly returning to normal after delivery. Testing for disorders in beta-oxidation of mitochondrial fatty acids did not reveal abnormalities in mother or child.
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PMID:Acute fatty liver in pregnancy. 1257 4

To elucidate the function of PPARgamma in leptin-deficient mouse (ob/ob) liver, a PPARgamma liver-null mouse on an ob/ob background, ob/ob-PPARgamma(fl/fl)AlbCre(+), was produced using a floxed PPARgamma allele, PPARgamma(fl/fl), and Cre recombinase under control of the albumin promoter (AlbCre). The liver of ob/ob-PPARgamma(fl/fl)AlbCre(+) mice had a deletion of exon 2 and a corresponding loss of full-length PPARgamma mRNA and protein. The PPARgamma-deficient liver in ob/ob mice was smaller and had a dramatically decreased triglyceride (TG) content compared with equivalent mice lacking the AlbCre transgene (ob/ob-PPARgamma(fl/fl)AlbCre(-)). Messenger RNA levels of the hepatic lipogenic genes, fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase-1, were reduced in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice, and the levels of serum TG and FFA in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice were significantly higher than in the control ob/ob-PPARgamma(fl/fl)AlbCre(-) mice. Rosiglitazone treatment exacerbated the fatty liver in ob/ob-PPARgamma(fl/fl)AlbCre(-) mice compared with livers from nonobese Cre(-) mice; there was no effect of rosiglitazone in ob/ob-PPARgamma(fl/fl)AlbCre(+) mice. The deficiency of hepatic PPARgamma further aggravated the severity of diabetes in ob/ob mice due to decreased insulin sensitivity in muscle and fat. These data indicate that hepatic PPARgamma plays a critical role in the regulation of TG content and in the homeostasis of blood glucose and insulin resistance in steatotic diabetic mice.
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PMID:Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. 1261 28

Dietary fish oil rich in (n-3) fatty acids plays an important role in reducing abnormalities associated with the metabolic syndrome and mortality from coronary heart disease. We investigated the effects of dietary fish oil on the metabolic syndrome in a high-sucrose-fed rat model. The model was achieved by the administration of 30% sucrose in drinking water in male Wistar rats during 21 weeks. After the metabolic syndrome rat model was established, fish oil was administered during 6 weeks. The metabolic syndrome rats showed significant increases in body weight, systolic blood pressure, serum insulin, total lipids, triacylglycerols, cholesterol, free fatty acids, LDL, total proteins, albumin, and serum tumor necrosis factor-alpha (TNF-alpha). They also presented abdominal and epididymal fat accumulation and fatty liver. After fish oil diet administration, metabolic syndrome rats had a significant reduction in blood pressure, serum insulin, triacylglycerols, cholesterol, free fatty acids, and total lipids, but no change was observed in TNF-alpha concentration or fat accumulation. In conclusion, fish oil reversed the alterations on metabolic parameters and blood pressure exerted by sucrose administration, although it had no effect on TNF-alpha production and adiposity. This confirms the theory that the molecular etiology of the metabolic syndrome is multifactorial, as is the effect of n-3 polyunsaturated fatty acids (PUFAs) upon it, having complex and multifaceted actions.
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PMID:Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor-alpha in rats with sucrose-induced metabolic syndrome. 1515 41

CCAAT/enhancer binding protein alpha (C/EBP alpha) is a critical factor in glucose metabolism in the neonate as revealed by conventional C/EBP alpha-null mice that do not survive beyond the first day after birth because of severe hypoglycemia and a deficiency in hepatic glycogen accumulation. To elucidate the function of C/EBP alpha in leptin-deficient mouse (ob/ob) liver, a C/EBP alpha-liver null mouse on an ob/ob background (ob/ob-C/EBP alpha/Cre(+)) was produced using a floxed C/EBP alpha allele and Cre recombinase under control of the albumin promoter (AlbCre). The C/EBP alpha-deficient liver in ob/ob mice had significantly decreased triglyceride content compared with equivalent mice lacking the AlbCre transgene (ob/ob-C/EBP alpha/Cre(-)). Expression of genes involved in lipogenesis including fatty acid synthase, acetyl-coenzyme A carboxylase, stearoyl-coenzyme A desaturase 1 and ATP-citrate lyase dramatically decreased in ob/ob-C/EBP alpha/Cre(+) mouse liver. Induction of these lipogenic genes by a high-carbohydrate diet caused an exacerbation in the development of fatty liver and an increase in liver size, hepatic triglyceride, and cholesterol contents in ob/ob-C/EBP alpha/Cre(-) mice but not in ob/ob-C/EBP alpha/Cre(+) mice. Deficiency in hepatic C/EBP alpha expression caused an exacerbation of hyperglycemia because of decreased insulin secretion. Taken together, these results indicate that hepatic C/EBP alpha plays a critical role in the acceleration of lipogenesis in ob/ob mice and in glucose homeostasis by the indirect regulation of insulin secretion.
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PMID:Hepatic CCAAT/enhancer binding protein alpha mediates induction of lipogenesis and regulation of glucose homeostasis in leptin-deficient mice. 1531 54

Serum interleukin-6 concentrations in patients with alcoholic liver disease Pathogenesis of alcoholic liver disease (ALD) is not well defined, but immune mediated hepatic injury is thought to be important. The main aim of this study was estimation of serum concentrations of IL-6 in patients with chronic alcoholic liver disease and determination of correlations between IL-6 serum concentration and occurrence of clinical manifestations, biochemical parameters and a stage of ALD. 85 patients with the diagnosis of chronic ALD and 35 healthy subjects (mached for age and sex) were enrolled into the study. Serum concentration of IL-6 was measured with ELISA. Serum IL-6 concentrations were markedly elevated in the all analyzed groups of patients with ALD when compared with healthy controls. When compared in groups, patients with alcoholic cirrhosis and chronic alcoholic hepatitis had the highest and patients with fatty liver had the lowest serum IL-6 concentrations. In addition, IL-6 concentrations were higher in patients with hepatic encephalopathy than in those without liver failure. Furthermore, we found statistically significant correlation between serum IL-6 and albumin concentrations. High IL-6 concentrations were associated with high mortality in patients with ALD. These findings suggest that IL-6 is an important immunological factor associated with alcoholic liver disease.
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PMID:[Serum interleukin-6 concentrations in patients with alcoholic liver disease]. 1562 53

Effects of glucocorticoids on lipid metabolism, hepatic metabolism, haematological parameters and milk yield in high-yielding cows in the early stages of lactation. The assumption is widespread that glucocorticoids promote lipolysis and fatty liver in ruminants. But there are contrary experimental results. Therefore we investigated the effects of dexamethasone (in the form of Voren suspension) in cows with very high milk yields (herd average 10.000 kg/year) between 7 and 15 days post partum, when high levels of lipolysis occur. Nine cows were given Voren 7 and 11 days post partum at doses of 0.02 mg/kg body weight. Glucose and insulin concentrations rose whilst FFA concentrations fell. Hepatic lipid levels were unchanged compared to a control group (n=8). There were also no changes in the various liver function parameters tested (beta-hydroxybutyrate, bilirubin, cholesterol, albumin, aspartat-amino-transferase, glutamat-dehydrogenase), which suggests that liver damage did not occur. Each of the two doses of Voren resulted in typical glucocorticoid-related changes in the differential leukocyte count. There was only a very slight reduction in daily milk yield. This studies show that, in ruminants, glucocorticoids have an indirect antilipolytic effect in vivo and do not aggravate or accelerate fatty degeneration of the liver.
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PMID:[Effects of glucocorticoids on parameters of lipid metabolism, hepatic metabolism, haematological parameters and milk yield in high-yielding cows in early lactation]. 1591 90

48 patients with alcoholic steatohepatitis (ASH) were examined and divided into 3 groups according to the degree of fatty liver infiltration. It was minimal in 8 (16. 6%) patients, moderate in 10 (20.8%) and severe in 30 (62.5%) patients. The higher the degree of the fatty infiltration, the more pronounced dystrophic alterations and the more often necrosis, fibrosis and cell infiltration focuses were found in liver biopsy material. Morphologic changes in biopsy samples from ASH patients were much more pronounced in comparison with those in non-alcoholic steatohepatitis (NASH). The latter is characterized mostly by lymphocyte infiltration, while leukocyte infiltration is more typical of ASH. The study found prominent alterations in serum lipoprotein spectrum, triglyceride (TG) and saturated fatty acid concentrations in patients with ASH. High concentrations of chylomicrons, low-density lipoproteins and TG were registered together with low levels of high-density lipoproteins and albumin complex.
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PMID:[Clinical and morphological features of alcoholic steatohepatitis]. 1594 Nov 41


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