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

Feeding large doses (30,000 IU/100 g body wt per day) of vitamin A to young rats for 2 days produced fatty liver, caused a stimulation of oxidation and esterification of [1-14C]palmitate by liver slices, and increased the activity of hepatic palmitoyl-CoA synthetase. Under similar conditions, however, release of hepatic triglycerides into the plasma, as judged from the post-Triton triglyceridemia, remained unaffected. It is indicated by the present findings that excessive intake of vitamin A produces fatty liver by stimulating the synthesis of triglycerides in liver without affecting the rate of secretion of hepatic triglycerides. An involvement of altered oxidation of fatty acids in the liver can also be ruled out because in hypervitaminosis A this process is increased rather than decreased as required for fatty liver production.
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PMID:Fatty liver in hypervitaminosis A: synthesis and release of hepatic triglycerides. 64 3

The catabolism of chylomicrons was investigated in genetically obese rats and their nonobese littermates, and was compared with catabolism in older Sprague-Dawley rats with body weights similar to the obese rats and their younger controls. Labeled thoracic-duct lymph was collected from donor rats and the catabolism of the labeled chylomicrons was studied after a single intravenous injection or during steady intravenous infusion in unanesthetized, nonfasting, recipient rats. In the genetically obese rats clearances from the plasma of chylomicron triacylglycerol and cholesteryl ester were less than in their nonobese littermates. Fractional clearance rates were reduced for both triacylglycerol and cholesteryl ester but triacylglycerol turnover rate (mg min(-1)) was greater than controls. Chylomicron triacylglycerol clearance was more efficient than cholesteryl ester clearance so that radioactivity remaining in the plasma was relatively depleted in triacylglycerol. The large-bodied old Sprague-Dawley rats showed no reduction in clearance of chylomicron radioactivity in comparison with younger controls. These results suggest that hyperlipidemia in genetically obese rats may be due in part to an accumulation of chylomicron remnants in the plasma. Flotation characteristics of plasma lipoproteins in the obese rats were consistent with this interpretation. However, separate experiments showed that genetically obese, fasting rats also accumulated more triacylglycerol in the plasma after injection of Triton WR 1339. The enlarged plasma triacylglycerol pool appears to derive from a mixture of hepatic and intestinal triacylglycerol-rich lipoproteins which, together, overload their common removal mechanism. Addition of cholesterol to the diets of the obese rats exacerbated their hyperlipemia and hepatic steatosis whereas their nonobese littermates and the large-bodied Sprague-Dawley rats were unaffected.
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PMID:Catabolism of chylomicron triacylglycerol and cholesteryl ester in genetically obese rats. 90 8

An experimental model for monitoring rat liver function during protracted exposure to hepatotoxic agents is proposed. Owing to their invasiveness, the models usually employed are appropriate for studying the mechanism of action of toxic substances, but do not allow the liver situation to be followed over the course of time. The need to sacrifice animals to determine liver triglycerides-one of the key parameters in the progress of toxic damage- reduces the possibility of following such progress in the same animals. This study describes the testing of a model for monitoring three basic parameters of liver injury: cytolysis, steatosis and metabolic deficiency of the liver. CCl4 has been chosen as model-hepatotoxin. Steatosis is determined by evaluating the triglyceride content of small specimens of liver, obtained through open-field biopsies, which appear to be representative of the whole liver. Fatty liver is paralleled by the block in Triton-induced hypertriglyceridaemia. Determination of serum triglycerides derives from a very poorly invasive technique which can be repeated several times. The combination of these tests with the assessment of both the cytolysis (ALT and SDH release into the circulation) and the impairment of the efficiency of liver microsomal enzymes (TMO clearance), seems to offer a reliable experimental procedure in predicting the hepatotoxic effect of xenobiotics.
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PMID:A model for monitoring changes in liver function. 379 13

Information regarding hepatic function during total parenteral nutrition in rats is often extrapolated to the clinical situation, but the steatosis observed in that species may simply reflect choline deficiency and be irrelevant to man. The effect of choline supplementation on hepatic lipid content and triglyceride secretion was examined in parenterally fed rats. Eighty to 90-day-old rats were randomized into three groups; group I received oral Purina Chow ad libitum, groups II and III received identical total parenteral nutrition regimens with the exception that group III received supplemental choline. After 7 days, peripheral triglyceride uptake was inhibited with Triton WR1339, the rate of secretion of 14C-labeled triglyceride measured after a bolus injection of 1-14C-palmitic acid, and total hepatic lipid content was measured. Total hepatic lipid content was elevated in group II (86.3 mg/g) and group III (83.3 mg/g), and both differed significantly from the control group I (35.2 mg/g, p less than 0.01), but the choline supplementation appeared to make no difference. Hepatic secretion of 14C-palmitic acid as 14C-triglyceride was reduced in group II (0.73%/ml plasma), and group III (0.72%/ml plasma) compared to group I (1.06%/ml plasma, p less than 0.05), and was unaffected by choline. The hepatic steatosis produced in the parenterally fed rat did not appear to be due to choline deficiency but to some other factors which may be important in man.
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PMID:The effect of choline supplementation on hepatic steatosis in the parenterally fed rat. 393 Jul 66

In rats, chronic ethanol feeding was found to enhance the postprandial hyperlipemia and to increase the incorporation of dietary palmitic acid-(3)H and intravenously injected L-lysine-(14)C into serum lipoproteins. The main increases of total amount, labeling, and specific activity of lipid and protein occurred in the d < 1.019 lipoprotein fraction. Fat absorption and the clearance of injected chylomicrons were not affected by ethanol feeding. Blocking of lipoprotein and chylomicron removal with Triton did not prevent the action of ethanol on serum lipids, indicating that the ethanol effect is not likely due to defective removal of lipids from the circulation. Ethanol enhanced the incorporation of chylomicron fatty acids into newly synthetized very low density lipoproteins, as shown by an increased reappearance of the fatty acid label into the lipids of this fraction after injection of palmitate-(14)C/glycerol-(3)H doubly labeled chylomicrons. These results indicate that alcoholic hyperlipemia is due, at least in part, to an increase in newly synthetized lipoproteins. The hyperlipemia produced by ethanol was accompanied by hepatic steatosis. The simultaneous production of fatty liver and hyperlipemia makes it unlikely that defective lipoprotein synthesis or secretion is a primary mechanism for the pathogenesis of the alcoholic fatty liver.
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PMID:Efcts of chronic ethanol feeding on serum lipoprotein metabolism in the rat. 544 77

After intravenous injection of palmitate-1-(14)C to rats fed a choline-deficient (CD) or choline-supplemented (CS) diet for 15-18 hr, liver triglycerides became labeled very rapidly. In CS, but not in CD rats, there was a considerable loss, with time, of radioactivity from liver triglycerides. At the same time, significantly less radioactivity appeared in plasma triglycerides of CD rats than of CS animals. No difference was seen in the triglyceride content of microsomes isolated from the liver of rats fed the two diets. The lower radioactivity in plasma triglycerides of CD rats was essentially due to a lower level and specific activity of very low density lipoprotein triglycerides. After intravenous injection of Triton and labeled palmitate, considerably less radioactivity accumulated in plasma triglycerides and phospholipids of CD rats than of CS animals. Post-Triton hyperphospholipidemia was also less pronounced in CD rats. It was concluded that the fatty liver observed in CD rats results from an impaired release of hepatic triglycerides into plasma.
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PMID:Choline-deficiency fatty liver: impaired release of hepatic triglycerides. 572 75

Hepatic steatosis frequently complicates total parenteral nutrition (TPN). Some of the mechanisms responsible were examined in rats receiving calories as dextrose (CHO-TPN) or dextrose plus lipid emulsion (Lipid-TPN). Hepatic triglyceride content increased approximately threefold after CHO-TPN and twofold after Lipid-TPN (P less than 0.02). Hepatic triglyceride fatty acid composition reflected endogenous synthesis. Hepatic acetyl-Coenzyme A carboxylase specific activity increased fourfold after CHO-TPN and twofold after Lipid-TPN, and it correlated positively with hepatic lipid content (r = 0.82). The activities of the microsomal enzymes of complex lipid synthesis were unchanged in the TPN groups. Both TPN regimens suppressed hepatic triglyceride secretion, measured by the rise in plasma triglyceride and the incorporation of [14C]palmitic acid into plasma triglyceride after intravenous Triton. Hepatic triglyceride secretion correlated negatively with total hepatic lipid content (r = -0.89). CHO-TPN increased the uptake of a radiolabeled triglyceride emulsion and increased hepatic lipase activity, whereas Lipid-TPN decreased both. Both adipose and cardiac lipase were higher for Lipid-TPN animals than for CHO-TPN or control animals. Hepatic 14C-triglyceride content was increased in both TPN groups as compared with controls after the injection of 1-[14C]-palmitic acid. This increment was proportional to the decreased hepatic secretion. Triglyceride fatty acid oxidation was significantly suppressed by CHO-TPN, less so by Lipid-TPN. Free fatty acid oxidation was suppressed only by CHO-TPN. The results suggest that the steatosis induced by TPN in rats was due to enhanced hepatic synthesis of fatty acid and reduced triglyceride secretion. Reduced hepatic triglyceride uptake, enhanced fatty acid oxidation, and enhanced peripheral tissue plasma triglyceride lipolysis when CHO-TPN is supplemented with lipid may modulate the accumulation of hepatic triglyceride and, along with reduced synthesis of fatty acid, lead to a lower hepatic triglyceride content.
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PMID:Pathogenesis of hepatic steatosis in the parenterally fed rat. 643 55

Male Japanese white rabbits were injected subcutaneously with methyl iodide (57 mg/kg body weight/day) on two successive days and their lipid metabolism was investigated 48 hr after the last injection. The plasma triglyceride levels increased from the preinjection average of 56.1 mg/dl to 246.0 mg/dl on an average, the individual values being greatly variable. Analysis of lipoprotein profile of plasma showed a significant increase of very low density lipoproteins (VLDL). Lipolytic activities in postheparin plasma did not change. However, rates of triglyceride secretion into plasma, measured by Triton WR 1339 injection method, were significantly higher in the animals treated with methyl iodide than in the controls. Histological investigation of the liver showed diffuse fat deposits in the hepatocytes without any destructive and inflammatory changes. The results indicate that hyperlipidemia and fatty liver of rabbits induced by methyl iodide is related to the elevation of triglyceride synthesis and its secretion in the liver.
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PMID:[Pathogenesis of hyperlipidemia and fatty liver of rabbits induced by methyl iodide. Increased synthesis and secretion of triglyceride in the liver]. 713 86

We previously showed that fatty liver was easily induced in suncus by starvation and that the plasma level of apolipoprotein B (apo B) was very low. There are three possible explanations for the low level of apo B in the animals: low synthetic rate, low secretion rate, and rapid catabolism in the circulation of apo B. We measured post-heparin lipolytic activity (lipoprotein lipase activity), which plays a key role in the catabolism of apo B-containing lipoprotein, VLDL, and found no difference between rats and suncus. We also investigated the hepatic synthetic rate of apo B by liver perfusion studies. Newly synthesized apo B in the suncus liver was detected by immunoprecipitation and found to amount to 12.5% of that in rats. The secretion rate of VLDL in suncus, which was estimated by intravenous injection of Triton WR1339, was 13.8% of that in rats. These two results suggest that there is no major defect in the secretory process. We separated Golgi apparatus from rat and suncus livers, and found much fewer lipoprotein particles in suncus than in rat Golgi apparatus. This evidence suggests that there is no defect in the lipolytic process or hepatic secretory process of apo B-containing lipoprotein, VLDL, but there may be a defect in the assembly process of VLDL and/or in the synthetic process of apo B in suncus. Such a defect may be one of the reasons for starvation-induced fatty liver in suncus.
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PMID:Defect in assembly process of very-low-density lipoprotein in suncus liver: an animal model of fatty liver. 759 40

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


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