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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 method has been developed to separate hepatocytes, isolated from laying hens, according to their densities, using discontinuous density-gradient centrifugation on Nycodenz. (2) The hepatocytes recovered from the interface of the 5% and 10% Nycodenz layers were rich in triacylglycerol and were termed 'fatty' hepatocytes: 'non-fatty' hepatocytes were obtained from the interface of the 15% and 30% Nycodenz layers and contained less than one-quarter as much triacylglycerol. (3) 'Fatty' hepatocytes incorporated radiolabelled glucose and glycerol into total lipid at more than twice the rate of 'non-fatty' cells: the corresponding increases in the incorporation of radiolabelled choline and valine into phospholipid and protein respectively were smaller and not statistically significant. (4) A higher proportion of glycerol and glucose incorporated into total lipid was found to be phospholipid in the 'non-fatty' hepatocytes. (5) A higher proportion of radiolabelled lipid or protein formed from glycerol or valine respectively was secreted into the medium by the 'non-fatty' hepatocytes. (6) The use of these hepatocytes as a model to study fatty liver syndromes is discussed.
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PMID:The use of two populations of hepatocytes with different triacylglycerol contents as a model to study the accumulation of liver lipid in the laying hen. 305 20

In an effort to determine if NMR techniques might be used to detect TPN-induced hepatic steatosis, the NMR spin-lattice (T1) and spin-spin (T2) relaxation times were measured on liver tissue from rats who received one of five dietary regimens: (1) 100% of nonprotein calories as lipid (Fat); (2) a mixture of 50% lipid and 50% glucose nonprotein calories (50/50); (3) 100% of nonprotein calories as glucose (CHO); (4) intravenous saline and standard laboratory rat chow (Saline); and (5) rat chow alone (Oral). The parenteral diets were isonitrogenous and isocaloric. Serum liver function tests were also measured. Animals in the Fat and 50/50 groups had the greatest amounts of liver fat and significantly longer T1 and T2 times (p less than 0.01) than any other group. Furthermore, the correlation of T2 time with liver fat content (r = 0.82) was far superior (p less than 0.001) to that of serum SGPT (r = 0.48) which was the only liver function test which correlated significantly with liver fat content. In a multiple linear regression analysis, T1 and T2 predicted liver fat content with an r value of 0.84 (p less than 0.001). These data suggest that in vivo NMR imaging techniques might be used to detect TPN-induced fatty infiltration of the liver noninvasively.
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PMID:Detection of total parenteral nutrition-induced fatty liver infiltration in the rat by in vitro proton nuclear magnetic resonance. 308 30

Total parenteral nutrition (TPN) is associated with hepatic biochemical and morphologic changes. Suggested causes include excessive glucose calories, fatty acid deficiency, and enterically derived hepatotoxins escaping atrophied bowel. Male Sprague-Dawley rats were cannulated or sham operated with internal jugular ligation. The cannulated groups received TPN with a 25% dextrose base, or TPN 12.5% dextrose and given nothing by mouth, or saline solution and allowed to eat ad lib. Sham animals ate ad lib. After 6 days the animals were killed and portal blood was assayed for endotoxin and cultured. Cultures were also taken of the liver. Serum hepatic enzyme concentration and hepatic fat were determined. All cultures and endotoxin assays were negative. Microscopy revealed nonlipid vacuolization in both TPN groups, a finding reproduced by direct portal infusion of endotoxin. There was significant hepatic steatosis in the 25% dextrose base TPN versus all other groups (28.6% liver weight versus 6.3% liver weight; p less than 0.05). This was correlated with caloric intake (28.7 calories/100 gm/day versus 21.2 calories/100 gm/day; p less than 0.05). Liver enzymes were not significantly different among groups. We conclude that hepatic steatosis in TPN is a result of overfeeding a glucose only substrate and that fatty infiltration is independent of changes in blood hepatic enzyme concentrations. Although other morphologic changes of hepatotoxin-induced injury were seen in the TPN group, portal endotoxemia to the level of 1 ng/ml could not be documented.
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PMID:Hepatic steatosis in total parenteral nutrition: failure of fatty infiltration to correlate with abnormal serum hepatic enzyme levels. 309 86

Although young infants are at greater risk for total parenteral nutrition (TPN)-related liver disease than adults, previous studies on the effect of the TPN energy source on the development of hepatic steatosis have been carried out in adult rats and adult humans. We studied the effect of a glucose and a glucose/fat TPN energy regimen on hepatic chemical composition and the development of steatosis in newborn miniature pigs. Twenty miniature pigs were randomized at 10 days of age to receive a TPN regimen which utilized either glucose (group A) or glucose/fat (group B) as the non-nitrogen energy source. After 8 days, blood was drawn for insulin, glucagon, SGPT, albumin, and bilirubin determinations. Samples of liver were obtained at 9 days. Plasma insulin levels were significantly higher and glucagon levels lower in group A piglets than in those in group B. Normal values were obtained for SGPT, albumin, and bilirubin, and no differences were found between groups. Chemical analysis of the livers revealed no differences between groups in the concentrations of glycogen, fat, protein, DNA, and RNA. Group A animals had significantly higher concentrations of water than group B (group A: 0.75 +/- 0.01 liter/kg; group B: 0.74 +/- 0.01; p less than 0.03). A significant correlation was found in group B between the plasma insulin/glucagon ratio and the hepatic glycogen concentration (r = 0.73, p less than 0.05). Group A animals had fat vacuoles in centrilobular hepatocytes, in contrast with group B animals who had visible fat only in Kupffer cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver composition and histology in growing infant miniature pigs given different total parenteral nutrition fuel mixes. 311 Apr 45

Hepatic steatosis is one of the two principal hepatic complications of total parenteral nutrition (TPN), the other being cholestasis. While the cause is uncertain, an excess of carbohydrate calories in rats leads to an elevated portal insulin/glucagon (I/G) molar ratio, periportal fatty infiltration, and increased total hepatic lipid content. Insulin causes fatty acid biosynthesis, whereas glucagon causes hepatic release and inhibition of fatty acid synthesis. Thus we attempted to add glucagon to lower the I/G to see if this would affect the degree of hepatic fatty infiltration by encouraging hepatic fat mobilization. Adult rats (n = 21) received internal jugular catheters; Group 1 (n = 7) was given saline solution (3 ml/h) and chow ad libitum; Group 2 (n = 7), 25% dextrose-base (D25W) TPN solution; Group 3 (n = 7), D25W TPN + 33 micrograms/100 gm/day glucagon. At 7 days portal and peripheral venous blood samples were drawn for insulin and glucagon radioimmunoassay and blood glucose determination; livers were removed for histologic study and lipid determination. Blood glucose did not differ in any group. Hepatic lipid and peripheral and portal venous I/G were increased and periportal fatty infiltration was extensive in Group 2, whereas hepatic lipid and I/G were decreased and periportal fatty infiltration was absent in glucagon-infused rats (Group 3). An abnormally high I/G ratio in portal blood elicited by high-glucose TPN may be responsible, at least in part, for hepatic steatosis. By increasing hepatic lipid export, addition of glucagon to TPN may play a major role in decreasing hepatic steatosis.
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PMID:Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. 313 27

The sulphur-containing drug, di-isopropyl-1,3-dithiol-2-ylidenemalonate (Malotilate) protects against the increase in hepatic triglyceride concentration after acute ethanol administration (either 6 g/kg p.o. or 2 g/kg i.p.) in rats. The compound had no influence on the increased hepatic NADH:NAD ratio (measured as the lactate:pyruvate and 3-hydroxybutyrate:acetoacetate ratios) after acute ethanol dosing (2 g/kg i.p.), but was found to lower hepatic acetaldehyde concentrations and prevent some of the disturbances in lipid metabolism observed in liver slices from ethanol-treated animals (e.g. decreased oxidation of [1-14C]palmitate to 14CO2) after this ethanol dose. The drug did not inhibit ethanol metabolism in this acute experiment. Administration of Malotilate to Wistar rats (100 mg/kg/day orally) during chronic feeding of ethanol as 36% of the total calorie intake in a liquid diet, resulted in a lower intake of the alcohol-containing diet by ethanol-fed animals and reduced body weight gain in rats which received the drug, without blood ethanol levels or the ethanol intake (expressed in g/kg body weight/day) being affected. In ethanol-fed animals, Malotilate prevented the production of fatty liver and the adaptive increase in the ethanol elimination rate (EER) normally seen in ethanol-fed animals, although the drug actually caused a slight increase in EER in glucose pair-fed controls. Malotilate did not significantly decrease the degree of induction of microsomal cytochrome P-450 by ethanol, but the increase in aniline hydroxylation was much less marked in animals receiving ethanol and Malotilate, suggesting that the activity of the inducible microsomal ethanol oxidising system (MEOS) may be reduced by the compound. Determination of hepatic acetaldehyde concentrations during ethanol feeding, and during an acute ethanol challenge test following long-term ethanol treatment showed that the compound significantly lowered the level of this ethanol metabolite in the liver under both circumstances. This reduction of hepatic acetaldehyde concentrations, probably resulting in part from the reduced EER as well as increased low-Km aldehyde dehydrogenase activities and glutathione contents seen in the livers of Malotilate-treated rats, are possible mechanisms by which the drug protects against triglyceride accumulation after ethanol administration.
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PMID:The effect of di-isopropyl 1,3 dithiol-2-ylidenemalonate (malotilate) on the hepatic changes induced by ethanol administration in the rat. 314 67

There are now nine inherited diseases that have been identified in the pathway of mitochondrial fatty acid oxidation, including LCAD, MCAD, SCAD, and HMG-CoA lyase deficiencies, two forms each of CPT and MAD deficiencies and an incompletely characterized disorder of primary carnitine deficiency. The varied range of clinical manifestations in this new group of diseases should attract the attention not only of general pediatricians (coma, hypoglycemia) but also of pediatric subspecialists in neurology (myopathy), cardiology (cardiomyopathy), and gastroenterology (fatty liver), as well as genetics and metabolism. The presenting features of the genetic defects in fatty acid oxidation fit well with the concept that fatty acid oxidation plays a major role in energy production during prolonged fasting and in working cardiac and skeletal muscle. Life-threatening episodes of coma and hypoglycemia induced by fasting are a common presenting feature in most of the fatty acid oxidation disorders (MCAD, LCAD, and HMG-CoA lyase deficiencies, the infantile form of CPT deficiency, the mild form of MAD deficiency, and in some cases of primary carnitine deficiency). The hypoglycemia in these disorders is most easily explained by the inability of affected patients to use fatty acids as a fuel as a substitute for glucose. It should be stressed, however, that the coma in these disorders may occur from direct toxic effects of fatty acids or fatty acid intermediates before plasma glucose concentrations reach hypoglycemic levels. Severe disturbances of muscle function are a feature in several of the disorders; hypertrophic cardiomyopathy and chronic skeletal muscle weakness occur in both the mild and severe forms of MAD deficiency, in primary carnitine deficiency, and in some patients with LCAD deficiency. In contrast, patients with the adult form of CPT deficiency have normal muscle strength but are prone to episodes of painful rhabdomyolysis induced by prolonged exercise. These manifestations presumably reflect the requirement of working cardiac and skeletal muscle for energy supplied from fatty acid oxidation. In two of the disorders, SCAD deficiency and the severe form of MAD deficiency, chronic CNS toxicity is a dominant feature. The severe effects on the brain in these two disorders may reflect the fact that short-chain fatty acids more readily cross the blood-brain barrier than longer-chain fatty acids.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New genetic defects in mitochondrial fatty acid oxidation and carnitine deficiency. 331 4

The role of the liver in glucose metabolism was investigated in 24 consecutive patients undergoing diagnostic liver biopsy by comparing hepatic morphometry and microsomal enzyme activity in vivo (antipyrine) with fasting blood glucose (BG) and immunoreactive insulin (IRI) levels and with the metabolic clearance rate of insulin and the insulin sensitivity index. The patients had elevated BG and IRI levels and reduced insulin-mediated glucose metabolism, insulin sensitivity index, and microsomal enzyme activity as compared with controls. The insulin metabolic clearance rate did not diverge among the groups. Patients with fatty liver had a high BG associated with a reduced glucose disposal rate, whereas fasting IRI did not diverge when compared with other liver patients. Glucose disposal rate was related to the amount of unaltered liver (r2 = 0.640; p less than 0.001) and antipyrine metabolism (r = 0.631; p less than 0.01) and inversely related to the amount of fat (r2 = 0.585; p less than 0.01). The findings demonstrate that insulin-mediated glucose metabolism is related to liver structure and microsomal function. Accumulation of fat in the liver seems to be a major factor associated with reduced insulin sensitivity and glucose tolerance.
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PMID:Insulin-mediated glucose metabolism is related to liver structure and microsomal function. 352 63

Coexistence of hyperinsulinemia and normal or impaired carbohydrate tolerance indicates insulin resistance which is frequently observed in patients with liver diseases such as liver cirrhosis, fatty liver, acute and chronic hepatitis and idiopathic haemochromatosis. Insulin resistance in liver diseases can be due to circulating insulin antagonists or a target tissue defect in insulin action, either due to changes in the state of the insulin receptor or due to a postreceptor defect, that means any abnormality in the insulin action sequence following the initial binding step. High insulin levels in liver diseases are caused by diminished degradation of insulin by the liver whereas hypersecretion only plays a minor role under basal conditions. High levels of glucagon, free fatty acids and growth hormone are well known in liver diseases but until now there is no evidence of the pathogenetic importance of these factors. Conflicting results on insulin binding, methodological criticism on binding data and the question whether or not diminished insulin binding on peripheral blood cells plays any physiological role make it unlikely that studies on insulin receptors of peripheral blood cells contribute to the revelation of insulin resistance in liver diseases. The clamp technique allows to quantify the sensitivity of the body to exogenous insulin. The results on liver cirrhosis in connection with studies on glucose metabolism show that under basal conditions insulin insensitivity is due to peripheral resistance (primarily muscle) according to a postreceptor defect. Finally the causes of insulin resistance in liver diseases are still not known.
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PMID:[Insulin resistance in liver diseases]. 353 94

A 54-year-old woman with obesity, type II diabetes mellitus, hyperlipidemia, and massive hepatomegaly was found to have severe steatosis and cirrhosis on liver biopsy. Complete evaluation led to the diagnosis of fatty cirrhosis associated with obesity and diabetic mellitus. She underwent four months of fasting with a protein-carbohydrate and vitamin-mineral liquid supplement to control her weight and metabolic abnormalities and to evaluate the effect of this diet on her liver disease. She lost 40 pounds to ideal body weight, normalized her serum glucose and lipids, and decreased total liver height by one third. Liver biopsy at the completion of her diet showed inactive cirrhosis and complete resolution of steatosis. Supplemented fasting with only modest weight loss can safely resolve fatty liver in obese diabetics with nonalcoholic steatosis and cirrhosis. Aggressive dietary approaches to achieve long-term weight loss deserve study in this subgroup of diabetics with unexplained chronic liver disease.
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PMID:Steatosis and cirrhosis in an obese diabetic. Resolution of fatty liver by fasting. 382 84


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