UMLS:C0015695 - FACTA Search

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Query: UMLS:C0015695 (fatty liver)
13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous report (Langner, C. A., Birkenmeier, E. H., Ben-Zeev, O., Schotz, M. C., Sweet, H. O., Davisson, M. T., and Gordon, J. I. (1989) J. Biol. Chem. 264, 7994-8003), we characterized the early developmental phenotype of mice that were homozygous for the autosomal recessive fatty liver dystrophy (fld) mutation. Shortly after birth, these mice can be distinguished from their +/? littermates by large pale livers, hypertriglyceridemia, elevations in hepatic apolipoprotein A-IV and apoC-II mRNA levels, and tissue-specific decreases in lipoprotein lipase and hepatic lipase activities. These traits resolve by the early weaning period. We have now characterized a second feature of this mutation: a peripheral neuropathy that becomes manifest by an abnormal gait at the end of the second postnatal week and persists through adulthood. Electron microscopic studies of sciatic nerves from 4-day-to 1-year-old fld/fld mice demonstrated a variety of abnormalities including thin, poorly compacted myelin sheaths, active myelin breakdown, and enlarged Schwann cell mitochondria and nuclei. Western blot analysis of sciatic nerve homogenates prepared from 1 to 3-month-old fld/fld mice and their +/? littermates indicated that homozygous animals have striking reductions in two peripheral nerve myelin-associated proteins, P0 and P2. The steady-state level of apoE, a protein induced during nerve regeneration, is markedly elevated. Furthermore, two axon-specific proteins, neurofilament 68K and growth-associated 43 protein, display altered expression in adult fld/fld sciatic nerves. High performance thin-layer chromatography revealed deficiencies in phospholipids, glycosphingolipids, and some neutral lipids in fld/fld sciatic nerves harvested during the first several months of life (compared to their +/? littermates). Cholesterol esters were elevated in homozygotes. By contrast, no differences in brain lipids were noted between fld/fld animals and their +/? littermates. These data suggest that the fld mutation is associated with an abnormality of myelin formation (dysmyelination) as well as demyelination and axonal degeneration that persists despite apparent resolution of the neonatal hypertriglyceridemia and associated lipase abnormalities. These findings establish the fld/fld mouse as an excellent model system for analyzing homeostatic mechanisms that modulate lipid metabolism in newborn mice and for examining the pathogenesis of peripheral neuropathies associated with dyslipidemias.
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PMID:Characterization of the peripheral neuropathy in neonatal and adult mice that are homozygous for the fatty liver dystrophy (fld) mutation. 205 Jun 89

Weanling male Hartley guinea pigs were fed for 6 weeks on a regular chow supplemented with 5% polyunsaturated fats (safflower, linseed, or evening primrose oil) or 5% saturated fats (hydrogenated coconut oil) with or without the addition of 1% cholesterol to the diet. Cholesterol feeding resulted in slower growth, hyperlipidemia, and a fatty liver. Cholesterol contents (predominantly in the form of cholesterol esters) in plasma and liver were increased, but the increase of plasma cholesterol was significantly reduced when unsaturated fats in place of saturated fat were added to the diet. The essential fatty acid contents in plasma and liver lipids were modulated by the dietary fats and by the cholesterol feeding. The latter reduced the proportions of 20:4 (n-6), but increased or had no effect on the levels of 18:2 (n-6). These results led to a reduced ratio of 20:4 (n-6)/18:2 (n-6), suggesting that cholesterol feeding may impair the desaturase activities.
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PMID:Effect of dietary cholesterol and polyunsaturated fats on plasma and liver lipids in guinea pigs. 382 3

Cholesterol, triglyceride, free fatty acid, and phospholipid concentrations were measured in 33 brain, liver, and adipose tissue samples obtained from 17 children who died of an acute encephalopathy associated with liver dysfunction and hyperammonemia (hyperammonemic encephalopathy). Eleven patients had Reye's syndrome, three had acute "toxic" encephalopathy (without fatty liver), two had glycogen storage disease type 1, and one had congenital hyperammonemia type 2. Hepatic triglyceride concentrations were markedly increased in Reye's syndrome, but varied from normal to increased concentrations in other hyperammonemic encephalopathies. In contrast, the acute encephalopathy could not be differentiated on the basis of clinical, laboratory, or pathologic features and the brain lipid profiles were remarkably similar among all patients studied.
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PMID:Tissue lipids in hyperammonemic encephalopathies of childhood. 692 60

Monkeys (Macaca nemestrina) were divided into four groups, and each group was fed a particular diet. The variables in the diets were as follows: diet A, 0.3 mg cholesterol/kcal nutrient; diet B, 1.0 mg cholesterol/kcal nutrient; diet C, 0.3 mg cholesterol/kcal nutrient, ethanol (36% of calories); diet D, 1.0 mg cholesterol/kcal nutrient, ethanol (36% of calories). Monkeys on the diets containing ethanol developed fatty liver. Mitochondria from ethanol-fed animals demonstrated significant decreases in uncoupler-stimulated, state 3, and state 4 succinate oxidation activity; respiratory control ratio; and ATP content. Liver microsomes isolated from the ethanol-fed groups demonstrated increased ethanol oxidizing activity with either NADPH or H2O2 as cosubstrate. Aniline hydroxylase and aminopyrine-N-demethylase activities were also elevated in ethanol-fed animals. The alterations in these functional properties were related primarily to ethanol in the diets. Cholesterol, while being less of a perturbant than ethanol, did elicit a significant decrease in cytochrome oxidase activity of mitochondria and a small but statistically significant increase in microsomal-associated ethanol oxidation activity. It appeared to potentiate the effect of ethanol in lowering mitochondrial respiratory control and ATP concentrations.
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PMID:Effect of dietary ethanol and cholesterol on metabolic functions of hepatic mitochondria and microsomes from the monkey, Macaca nemestrina. 702 93

Monkeys (Macaca nemestrina) were divided into four groups, and each group was fed a particular diet. The variables in the diets were as follows: diet A, 0.3 mg cholesterol/kcal nutrient; diet B, 1.0 mg cholesterol/kcal nutrient; diet C, 0.3 mg cholesterol/kcal nutrient, ethanol (36% of calories); diet D, 1.0 mg cholesterol/kcal nutrient, ethanol (36% of calories). Monkeys on the diets containing ethanol developed fatty liver. Mitochondria and microsomes isolated from these livers demonstrated ethanol-elicited alterations in metabolic functions as is described in the preceding paper. Accompanying these changes in metabolic activities were alterations in organelle phospholipids that were influenced by both dietary ethanol and cholesterol. The changes that could be attributed to ethanol were as follows. Phosphatidyl ethanolamine was decreased in microsomes and increased in mitochondria; the sphingomyelin content in microsomes was increased significantly. The levels of stearic and arachidonic acid were elevated, and palmitic and oleic acid decreased, in phospholipids from both mitochondria and microsomes. Cholesterol influenced the fatty acid composition of several phospholipids, usually in a direction opposite to those alterations attributed to ethanol. Cholesterol feeding increased levels of palmitic and oleic acid and decreased amounts of stearic, linoleic, and arachidonic acid in several phospholipids. The significant ethanol- and cholesterol-elicited alterations observed in this study suggest the possibility that the changes in metabolic functions in mitochondria and microsomes are controlled, at least in part, by alterations in the phospholipid compositions of these organelles.
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PMID:Effect of dietary ethanol and cholesterol on phospholipid composition of hepatic mitochondria and microsomes from the monkey, Macaca nemestrina. 702 94

We have previously shown that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apoB) was very low. We also previously reported that a defect in the assembling process of apo B-containing lipoprotein (very low density lipoprotein, VLDL) may be one of the reasons for the low level of plasma apo B and for induction of fatty liver by starvation in suncus. We also found that hepatic acyl coenzyme A cholesterol acyltransferase (ACAT) activity is very low in the animals, resulting in decreased cholesteryl ester contents in the liver. A deficiency of cholesteryl ester in suncus liver may be one of the reasons for the defect in the assembling process of VLDL. In this study, we investigated the effect of cholesterol-feeding, which induces an increase in triglyceride and cholesteryl ester of the liver as a consequence of the induction of both intestinal and hepatic ACAT activities, on the secretion of VLDL. Although the basal ACAT activity of intestinal mucosa was high, cholesterol-feeding did not induce either an increase in plasma lipid or an increase in intestinal ACAT activities in suncus. The hepatic secretion rate of VLDL was estimated by treatment with Triton WR1339, which is well known to inhibit the catabolism of VLDL. Cholesterol-feeding caused a slight increase in hepatic triglyceride and cholesteryl ester but no increase either in the secretion rate of VLDL or in hepatic ACAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of acyl coenzyme A cholesterol acyltransferase in intrahepatic processing of apo B-lipoprotein in suncus. 854 56

Based on studies that show a role for the low-density lipoprotein (LDL)-receptor in arachidonic acid delivery and eicosanoid synthesis in macrophages, the present study investigated the effect of cholesterol supplementation on pathological changes and thromboxane (TX) synthesis in alcoholic liver injury. Male Wistar rats were intragastrically fed ethanol with either corn oil or fish oil for 1 month. Control rats received isocaloric amounts of dextrose instead of ethanol. An additional group of rats fed either ethanol or dextrose with fish oil or corn oil were supplemented with 1% cholesterol. At the time of killing, all rats had the following evaluated: liver histopathology, lipid peroxidation, liver and plasma thromboxane levels, plasma endotoxin and messenger RNA (mRNA) levels of LDL-receptor, tumor necrosis factor alpha (TNF-alpha), cyclooxygenase (Cox)-1 and -2, and transforming growth factor beta (TGF-beta). Rats fed ethanol with either fish oil or corn oil developed fatty liver, necrosis, inflammation, and central vein collagen deposition. Cholesterol supplementation enhanced the degree of fibrosis but prevented necrosis and inflammation. These alterations in pathological changes by cholesterol were accompanied by absent TNF-alpha and Cox-2 mRNAs, decreased thromboxane levels, decreased lipid peroxidation, and increased TGF-beta mRNA. Cholesterol enrichment of the diet thus decreases proinflammatory components, but enhances fibrosis in ethanol-fed rats.
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PMID:Cholesterol supplementation prevents necrosis and inflammation but enhances fibrosis in alcoholic liver disease in the rat. 921 56

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

The purpose of this study was to modify the amount of 22:4 n-6, 22:5 n-6 and 20:5 n-3 in cardiac phospholipids and to evaluate the influence of these changes on the functioning of working rat hearts and mitochondrial energy metabolism under normoxic conditions and during postischemic reperfusion. The animals were fed one of these four diets: (i) 10% sunflower seed oil (SSO); (ii) 10% SSO + 1% cholesterol; (iii) 5% fish oil (FO, EPAX 3000TG, Pronova) + 5% SSO; (iv) 5% FO + 5% SSO + 1% cholesterol. Feeding n-3 PUFA decreased n-6 PUFA and increased n-3 PUFA in plasma lipids. In the phospholipids of cardiac mitochondria, this dietary modification also induced a decrease in the n-6/n-3 PUFA ratio. Cholesterol feeding induced marked hepatic steatosis (HS) characterized by the whitish appearance of the liver. It also brought about marked changes in the fatty acid composition of plasma and mitochondrial phospholipids. These changes, characterized by the impairment of deltaS- and delta6-desaturases, were more obvious in the SSO-fed rats, probably because of the presence of the precursor of the n-6 family (linoleate) in the diet whereas the FO diet contained large amounts of eicosapentaenoic and docosahexaenoic acids. In the mitochondrial phospholipids of SSO-fed rats, the (22:4 n-6 + 22:5 n-6) to 18:2 n-6 ratio was decreased by HS, without modification of the proportion of 20:4 n-6. In the mitochondrial phospholipids of FO-fed rats, the amount of 20:5 n-3 tended to be higher (+56%). Cardiac functioning was modulated by the diets. Myocardial coronary flow was enhanced by HS in the SSO-fed rats, whereas it was decreased in the FO-fed animals. The rate constant k012 representing the activity of the adenylate kinase varied in the opposite direction, suggesting that decreased ADP concentrations could cause oxygen wasting through the opening of the permeability transition pore. The recovery of the pump function tended to be increased by n-3 PUFA feeding (+22%) and HS (+45%). However, the release of ascorbyl free radical during reperfusion was not significantly modified by the diets. Conversely, energy production was increased by ischemia/reperfusion in the SSO group, whereas it was not modified in the FO group. This supports greater ischemia/reperfusion-induced calcium accumulation in the SSO groups than in the FO groups. HS did not modify the mitochondrial energy metabolism during ischemia/reperfusion. Taken together, these data suggest that HS- and n-3 PUFA-induced decrease in 22:4 and 22:5 n-6 and increase in 20:5 n-3 favor the recovery of mechanical activity during post-ischemic reperfusion.
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PMID:Effects of dietary polyunsaturated fatty acids and hepatic steatosis on the functioning of isolated working rat heart under normoxic conditions and during post-ischemic reperfusion. 1169 87

Naringin, a bioflavonoid found in citrus fruit peel, is known to have an antioxidative effect, but its effect on atherosclerosis has not been studied. This study evaluated the effect of naringin on blood lipid levels and aortic fatty streaks, and its action mechanism in hypercholesterolemic rabbits. Male New Zealand white rabbits were fed a 0.25% cholesterol diet and divided into an untreated group (n = 4), a naringin-treated group (n = 5; 500 mg/kg per day), and a lovastatin-treated group (n = 5; 20 mg/kg per day). After 8 weeks, blood was sampled and analyzed biochemically. Aorta and liver were harvested and examined histologically. Cholesterol level in rabbits fed the 0.25% cholesterol diet reached 17 times normal and decreased in the rabbits fed naringin and lovastatin, whose effects were not statistically significant (p > 0.05). However, both naringin and lovastatin effectively decreased the area of fatty streak in thoracic aorta on macroscopic analysis (p < 0.05) and significantly reduced subintimal foam cell infiltration on microscopic morphometry (p < 0.05). These foam cells were macrophages on immunohistochemical analysis. Naringin treatment inhibited hypercholesterolemia-induced intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells. Hypercholesterolemia caused fatty liver and elevation of liver enzymes, which was prevented by naringin but not by lovastatin. Naringin significantly reduced fatty streak formation and neointimal macrophage infiltration and also inhibited the expression of ICAM-1 in endothelial cells, suggesting that suppression of ICAM-1 contributed to the antiatherogenic effect. Naringin, unlike lovastatin, has a hepatoprotective action.
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PMID:Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits. 1170 99

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