Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isopropanol and acetone administered to rats in conditions leading to a similar blood acetone level differ markedly in their effects on lipid metabolism. Isopropanol administration determines a fatty liver, which is mainly related to a defect in hepatic lipoprotein synthesis. Acetone administration gives only raise to a slight increase in the liver triacylglycerol level. It does not alter the [1-14C] palmitate, [1-14C] glycerol or [U-14C] leucine incorporation into blood lipoproteins. Acetone does thus not appear to play a preminent role in the isopropanol induced fatty liver which seems to be related mainly to a direct action of the alcohol itself.
 ...
PMID:[Comparison of the effect of acetone and isopropanol on lipid metabolism in rats]. 7 72

The acute effects of the PCB (polychlorinated biphenyls) mixture (Aroclor 1254) on microsomal enzymes and on synthesis and turnover of microsomal and cytoplasmic lipids of rat liver were investigated. Six daily i.p. injections of 25 and 50 mg PCB/kg body weight resulted in increased liver weight and liver to body weight ratios. When compared to controls PCB treatment resulted in a six-fold increase in amount of cytochrome P-450. Activities of NADPH-cytochrome c reductase, ethylmorphine demethylase and inosine diphosphatase were increased whereas glucose-6-phosphatase values were decreased by PCB exposure. Analysis of liver homogenate and microsomal fraction revealed an increase in lipid in PCB-exposed animals. Phospholipids, cholesterol and triglyceride were significantly increased after PCB exposure; however, the greatest percentage increase was seen in the triglyceride pool. The finding of an increase in microsomal triglyceride to phospholipid ratios with exposure to PCB is suggestive of an increase in membrane-enclosed lipid (liposomes). Studies with labelled glycerol indicated that the PCB-induced fatty liver resulted from increased half life but not increased synthesis of liver lipid moieties. The rate of incorporation of leucine into microsomal membrane and albumin was somewhat enhanced in rats exposed to PCB indicative of increased protein synthesis. Morphological studies showed increased occurrence of lipid material, both in cytoplasmic droplets and within rough and smooth-surfaced endoplasmic reticulum. Proliferation of smooth endoplasmic reticulum and flattened Golgi cisternae with no secretion granules containing lipoprotein particles characterized the liver from animals exposed for 6 days. The increase in lipid within membranes of the endoplasmic reticulum together with the flattened Golgi lacking typical secretory vesicles indicates a defect in transport of lipoproteins from the endoplasmic reticulum to the Golgi apparatus and may be the cause of the PCB-induced fatty liver.
 ...
PMID:Studies on the cellular toxicity of polychlorinated biphenyls (PCBs). I. Effect of PCBs on microsomal enzymes and on synthesis and turnover of microsomal and cytoplasmic lipids of rat liver- a morphological and biochemical study. 9 1

Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VLDL) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL, secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [(3)H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apoVLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are separated by polyacrylamide gel electrophoresis. Similar patterns are noted when non-recirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation.
 ...
PMID:Secretion of cholesterol-rich lipoproteins by perfused livers of hypercholesterolemic rats. 22 14

The authors' previous studies have shown that hepatic steatosis of chronic ethanol ingestion in rats can be prevented by adding pyruvate, dihydroxyacetone, and riboflavin to their diet. In this study, the authors investigated the effect of chronic ethanol ingestion, with or without addition of the above metabolites to the diet, on protein and amino acid concentrations in tissues. Rats (120 g) were divided into three groups and fed isocalorically one of the fellowing diets for 30 days: control diet (28% fat, 15% protein, and 57% carbohydrate), ethanol diet (28% fat, 15% protein, 23% carbohydrate, and 24% ethanol), and metabolite diet (ethanol diet plus pyruvate, dihydroxyacetone, and riboflavin). Chronic ethanol ingestion reduced growth of muscle and intestinal mucosa without affecting that of liver and kidney. Among the 15 amino acids measured, chronic ethanol ingestion had the most consistent effect on plasma and tissue concentrations of leucine, alanine and alpha-amino-n-butyrate. The concentration of leucine was increased in muscle, liver, and plasma; that of alpha-amino-n-butyrate was increased in muscle and plasma, whereas that of alanine was decreased in plasma and liver. Addition of pyruvate, dihydroxyacetone, and riboflavin to the ethanol diet either totally or partially prevented ethanol-induced changes in plasma and tissue concentrations of amino acids despite similarity in plasma ethanol levels. Although these metabolites prevented the inhibition of the growth of intestinal mucosa, they were ineffective in blunting the effect of ehtanol on the skeletal muscle. This latter observation suggests that the mechanism of ethanol-induced inhibition of tissue growth is not the same for these tissues.
 ...
PMID:Prevention of effects of ethanol on amino acid concentrations in plasma and tissues by hepatic lipotropic factors in rats. 75 34

The effect of chronic exposure to micromolar concentrations of Aroclor 1254 (Aro) on the hepatic lipid metabolism was studied in long-term cultures of adult rat hepatocytes. Hepatocytes were cocultivated with mitomycin C-treated 3T3 cells and exposed for 2 wk to Aroclor 1254 concentrations ranging from 0.01 to 20 micrograms/ml. The Aro-exposed cultures showed intracytoplasmic lipid droplets and a maximum increase of 55% in the triglyceride (TG) content and of 4.4-fold in the cytochrome P-450 content. Labeling studies with [14C]acetic and [14C]oleic acid showed no changes in the uptake of fatty acid and TG precursors by the Aro-treated cultures; the synthesis of cellular lipids from [14C]acetic acid was slightly inhibited by Aroclor 1254, but that from [14C]oleic acid was increased, specially for TG (37%). The secretion of total lipids and TG was 2.1- and 2.7-fold lower, respectively, in the cultures treated with 20 micrograms/ml of Aroclor 1254, resulting in an increase of 1.9-fold in the intracellular content of TG. The synthesis of cellular proteins labeled with [3H]leucine was unchanged in the Aro-treated cultures, but the secretion of exportable proteins was 1.7-fold lower in the cultures treated with 20 micrograms/ml of Aroclor 1254. Our results showed that long-term exposure to in vivo relevant concentrations of Aroclor 1254 produced morphological and biochemical changes in cultured hepatocytes, like those described in vivo, and intracellular TG accumulation due mostly to impaired secretion of TG by the hepatocytes. Our results also suggest that this culture system could be useful for the screening of toxic agents producing fatty liver and the study of the involved mechanism(s).
 ...
PMID:Triglyceride accumulation in long-term cultures of adult rat hepatocytes by chronic exposure to Aroclor 1254. 249 54

Trifluoperazine (TFP) (50 mg/kg ip) administration to rats 6 or 10 hr after CCl4 (1 ml/kg ip in olive oil) significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as evidenced by either histology or electron microscopy. TFP given 6 hr after CCl4 significantly decreased the CCl4-induced increases in liver calcium content. TFP raised four to five times the liver glycogen content in control rats but was unable to modify decreased glycogen content of CCl4 poisoned animals. TFP administration increased phospholipid and protein synthesis as evidenced by studies on 32P incorporation into microsomal phospholipid and by experiments on [14C]leucine incorporation in microsomal protein fractions from control rat livers. No significant changes were observed in microsomal phospholipid degradation as studied by decay of label from 32P-prelabeled microsomal lipids or in increased protein degradation as evidenced by decay of label from [14C-guanidino]arginine-prelabeled microsomal proteins found in livers of control rats after TFP treatment. Electron microscopy observations of liver from control animals treated with TFP evidenced accumulation of glycogen in areas close to smooth endoplasmic reticulum (SER); large Golgi areas with an abundant number of lysosomes, and minor dilatation effects on the rough endoplasmic reticulum (RER) and nuclear membrane. Results suggest that TFP preventive effects might be due to the anticalmodulin actions of this drug.
 ...
PMID:Further studies on the late preventive effects of the anticalmodulin trifluoperazine on carbon tetrachloride-induced liver necrosis. 337 54

Young rats were force-fed a lysine + arginine-devoid diet or a complete diet for 3 days, and selected biochemical and morphologic studies were conducted. Rats force-fed the experimental diet in comparison with those force-fed the control diet for 3 days showed decreased body weight gain, hepatomegaly with periportal fatty liver, pancreatic and splenic atrophy, and enhanced 14C-leucine incorporation into hepatic proteins. Differences in the experimental animals were observed in the free amino acid levels of serum (decreased lysine, arginine, and ornithine) and liver (decreased ornithine), in blood chemistries (decreased levels of ammonia N2, uric acid, cholesterol, protein, albumin, alkaline phosphatase, LDH and SGOT) and in hematologic findings (leukocytopenia and thrombocytopenia after a morning feeding). The experimental findings in young rats force-fed the lysine + arginine-devoid diet were compared with those reported to develop in children with lysinuric protein intolerance (LPI), an autosomal recessive defect in diamino acid transport. Children with LPI as described by others reveal a number of similarities as well as a number of differences in comparison to the findings in the experimental animals. The comparison suggests that some of the pathological manifestations of LPI may be related to a deficiency of diamino acids but others must be due to different alterations in this complex human disease.
 ...
PMID:Chemical pathology of diamino acid deficiency: considerations in relation to lysinuric protein intolerance. 393 96

Baboons fed ethanol (50% of total calories) chronically develop ultrastructural alterations of hepatic mitochondria. To determine whether mitochondrial functions are also altered, mitochondria were isolated from nine baboons fed ethanol chronically and their pair-fed controls. At the fatty liver stage, ADP-stimulated respiration was depressed in ethanol-fed baboons by 59.4% with glutamate, 43.2% with acetaldehyde, 45.1% with succinate and 51.1% with ascorbate as substrates. A similar decrease was noted in the ADP/O ratio (14 to 28%) and respiratory control ratio (20 to 44%) with all substrates. Similar alterations of mitochondrial functions were observed in baboons with more advanced stages of liver disease, namely fibrosis. These changes after ethanol treatment were associated with decreases in the enzyme activities of mitochondrial respiratory chain: glutamate, NADH and succinate dehydrogenase (42, 24 and 28%, respectively), glutamate-, NADH- or succinate-cytochrome c reductase (42, 27 and 32%, respectively) and cytochrome oxidase (59.6%). The content of all cytochromes was also decreased in ethanol-fed baboons, especially aa3 (57%). Moreover, [14C]leucine incorporation into mitochondrial membranes was depressed by 21% after ethanol treatment. On the other hand, glutamate dehydrogenase activities of serum and cytosol in ethanol-fed baboons were significantly higher than those in pair-fed controls. Morphologically, mitochondria of ethanol-fed baboons were larger than those of pair-fed controls. However, the mitochondrial protein content per mitochondrial DNA was unchanged. From these results, we conclude that, morphologically and functionally, hepatic mitochondria in baboons are altered by chronic ethanol consumption; it is noteworthy that these changes are fully developed already at the fatty liver stage, and that morphological alteration appears to reflect the damage of mitochondrial membranes rather than an adaptive hypertrophy.
 ...
PMID:Biochemical and morphological alterations of baboon hepatic mitochondria after chronic ethanol consumption. 653 46

A method has been developed to measure the in vitro production of immunoglobulin (Ig) by liver biopsy specimens. Five to 30 mg of liver tissue was cultured for 24 h in Dulbecco's modified Eagle's medium/10% foetal calf serum (FCS) containing radiolabelled leucine (L-[4,5-3H] leucine). The culture medium was collected, centrifuged and the supernatant dialysed to remove labelled leucine. The residual radioactivity was a measure of newly synthesized 3H-labelled proteins released into the medium. The quantity of IgG was determined by immunoprecipitation with monospecific antisera to IgG heavy chains. The presence of IgG in the supernatant was confirmed by chromatography on protein-A Sepharose column. In 6 biopsies without evidence of active inflammation (4 normal and 2 fatty liver by histological criteria) less than 1% of the protein synthesized was IgG. In contrast in the presence of active inflammation in 4 cases of alcoholic hepatitis the IgG percentage ranged from 2 to 6%. Maximal levels of IgG production were detected in 3 cases of chronic active hepatitis (CAH) and ranged from 5 to 30%. The increased Ig synthesis by the liver in alcoholic hepatitis and CAH is presumed to be an index of the intrahepatic host response and may have important implications for mechanisms of liver damage in these diseases.
 ...
PMID:Intrahepatic synthese of immunoglobulin G in chronic liver disease. 719 89

The therapeutic effect of diisopropyl 1,3-dithiol-2-ylidenemalonate (NKK-105) on the fatty liver induced by carbon tetrachloride (CCl4) was studied. The recovery from elevated liver triglyceride levels induced by CCl4 required over 20 days in 35 week-old rats, but 14 days in 6 week-old rats. This indicates that 35 week-old rats are useful for studying the therapeutic effect of NKK-105 on fatty liver. In rats with CCl4-induced fatty liver, NKK-105 lowered the hepatic triglyceride level, accelerated the rate of triglyceride release from the liver, enhanced the incorporation of 14C-leucine into microsomal protein, and increased the RNA content in microsomes. These data suggest that NKK-105 exerts a curative effect on CCl4-induced fatty liver by improving the impaired protein synthesis and by promoting lipoprotein secretion.
 ...
PMID:Effect of diisopropyl 1,3-dithiol-2-ylidenemalonate (NKK-105) on fatty liver induced by carbon tetrachloride. 725 41


1 2 3 4 5 Next >>