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)

A model has been developed for the administration to rats and baboons of ethanol as part of a nutritionally adequate liquid diet. With this regimen, ethanol intake was much higher than with conventional procedures. All animals gained or maintained their body weight, and liver morphology was normal in the controls. Isocaloric substitution of carbohydrate by ethanol (36% of total calories in rats and 50% in baboons) resulted in the production of fatty liver in all animals, while the baboons also developed alcoholic hepatitis and cirrhosis with increased activities of serum glutamic oxaloacetic transaminase. Inebriation and manifestation of dependence upon withdrawal of the diet were observed in baboons and quantitated in the rat. Chemical alterations produced by ethanol at the fatty liver stage were characterized by hyperlipemia, striking triglyceride accumulation in the liver and enhanced activities of microsomal drug metabolizing enzymes, including the microsomal ethanol oxidizing system (MEOS). Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis), and differed strikingly from the alterations produced by other models of liver injury. In showing that all aspects of liver injury observed in alcoholics can be reproduced in animals by the feeding of pure ethanol with an adequate diet, this study incriminates ethanol itself as a cause for the hepatic complications. This new experimental model is proposed as a tool for the study of the pathogenesis and treatment of alcoholic liver injury and dependence.
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PMID:Alcoholic liver injury: experimental models in rats and baboons. 123 25

The present study deals with a case of hepatic parenchymal steatosis in a child with primary ciliary dyskinesia (immotile cilia syndrome) well documented by functional and ultrastructural evaluation of the ciliary epithelia. Hepatic steatosis was associated with ultrastructural evidence of retention of material either in the cisternae of the endoplasmic reticulum or in proximity of the Golgi apparatus of hepatocytes. It is suggested that the absence of dynein in the axoneme is probably part of a diffuse genetic defect which may extend to cytoplasmic, non axonemal, dynein and lead to a disturbance of various microtubule-dependent cell activities.
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PMID:Steatosis associated with immotile cilia syndrome: an unrecognized relationship? 150 Jun 95

The complex distribution of polychlorinated biphenyl (PCB) isomers and congeners amongst plasma fractions of the pigeon suggests that the lipid and apolipoprotein components of lipoproteins, as well as plasma proteins, may be important in transporting PCBs to tissues (Borlakoglu et al., Biochem. Pharmac. 40, 265 (1990]. Pigeons were injected with the commercial PCB mixture Aroclor 1254 (1.5 mmol/kg body weight). After 120 hr triacylglycerol-like droplets accumulated in hepatocytes ('fatty liver syndrome'), there was proliferation of the hepatic smooth endoplasmic reticulum, and plasma concentrations of triacylglycerol and total cholesterol increased. This was accompanied by significant decreases in plasma concentrations of total protein, total apolipoproteins of the low density lipoprotein (LDL) and the high density lipoprotein (HDL) fractions, and albumin and by a significant increase in that of urea, indicating increased protein breakdown. These results suggest that Aroclor 1254 increased hepatic lipid synthesis, but decreased hepatic production of albumin and apolipoproteins. This would explain the accumulation of triacylglycerol in the liver and the increase in the proportion of triacylglycerol to apolipoprotein in the total lipoproteins. From the evidence presented, a model is proposed based on the association of PCBs with hydrophobic domains of lipids and proteins for the transport of PCBs by plasma fractions, their uptake into cells and intracellular metabolism, and their accumulation in adipose tissue.
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PMID:Transport and cellular uptake of polychlorinated biphenyls (PCBs)--II. Changes in vivo in plasma lipoproteins and proteins of pigeons in response to PCBs, and a proposed model for the transport and cellular uptake of PCBs. 211 78

The liver is the main organ for alcohol metabolism and is therefore predisposed for various functional changes and irreversible alterations. The alcoholic fatty liver represents the early stage of alcohol-induced liver diseases and is completely reversible upon consequent alcohol abstinence. Already at this early stage a significant increase of gamma-glutamyltransferase activities is commonly found in the serum, which can mainly be attributed to an enzyme induction in the endoplasmic reticulum of the liver cell. Other stages of alcohol-induced liver diseases include the alcoholic hepatitis and the liver cirrhosis, which have a better prognosis upon consequent alcohol abstinence compared to continuous alcohol consumption. Many therapeutic studies with various drugs have been carried out in patients with alcohol-induced liver diseases, but at present a treatment with drugs in a sufficiently great number of patients has not been firmly established. The most important medical goal is to establish the diagnosis of alcohol-induced liver diseases already at the early stage of the fatty liver in order to initiate the necessary therapeutic measures with the aim of a consequent alcohol abstinence.
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PMID:[The liver and alcohol]. 285 Jun 81

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.
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PMID:Further studies on the late preventive effects of the anticalmodulin trifluoperazine on carbon tetrachloride-induced liver necrosis. 337 54

Ultrastructural study of hepatic parenchyma was carried out in female Wistar rats after they had received high doses (400 mg X kg-1) of rifampicin for 1, 2, 4, 6 and 8 days. Morphological changes in the endoplasmic reticulum, Golgi apparatus and mitochondria were observed as early as day 1 of intoxication. These changes corroborate the biochemical data available regarding RFP-induced fatty liver.
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PMID:Ultrastructural changes in the parenchymal liver cells of rats treated with high doses of rifampicin. 358 Feb 80

The ultrastructure of the liver in normal, mildly ketotic and severely ketotic cows was studied using stereological methods. In the liver of severely ketotic cows there is: (1) a significant increase in the volume fraction of hepatocytes and a decrease in the volume fraction of sinusoids, and (2) an increase in the volume fraction of lipid and smooth endoplasmic reticulum and a decrease in the volume fraction of glycogen and Golgi in parenchyma. A decrease in the profile density of mitochondria per 1 mm2 field and an increase of the volume occupied by mitochondria were not significant nor was the decrease in the volume density of rough endoplasmic reticulum. The degree and duration of negative energy balance obviously affect the morphological changes of the fatty liver. However, additional work is needed to determine the significance of ultrastructural changes in liver function.
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PMID:Ultrastructural changes of the liver in spontaneously ketotic cows. 403 Nov 38

Ultrastructural alterations of 4-aminopyrazolopyrimidine (4-APP)-induced fatty liver were studied. Light microscopically, liver sections after 3 to 5 days of 4-APP administration demonstrated more extensive fatty changes and highly osmiophilic lipid droplets were mainly observed in the portal zones of the lobules. The most striking ultrastructural alterations were seen in the Golgi complexes and rough endoplasmic reticulum. Golgi complexes were markedly dilated and osmiophilic vesicles were noted near the Golgi complexes. In the rough endoplasmic reticulum, dilatation of cisternae, loss of the parallel arrangement and dilated vesicles, most of which contained diminished numbers of ribosomes, were also seen. In addition, degranulation of rough endoplasmic reticulum was observed. However, no remarkable changes were noted in the mitochondria. Based on these findings, the functional state of the organellae concerned was discussed.
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PMID:Ultrastructural studies in 4-aminopyrazolopyrimidine (4-APP)-induced fatty liver. 409 13

This study provides confirmation of previous observations that showed that rats fed a diet containing 1% orotic acid for 7 days develop a fatty liver and that there is an inhibition of the secretion of low density lipoproteins without altering general liver protein synthesis. Accumulated fat droplets (liposomes) are entrapped within rough endoplasmic reticulum vesicles. In this study, these vesicles have been shown to accumulate the apolipoproteins of low and very low density lipoproteins. Inhibition of lipoprotein secretion was demonstrated by perfusion of livers from orotic acid-fed rats with a serum-free medium. Liposomes were isolated from these rats. Partially delipidated liposomes, but not similarly treated microsomes or cell sap, were found to form a precipitation line when reacted against anti-low density lipoprotein antiserum. Detergent solubilization of the liposome followed by density gradient centrifugation resulted in a peak at d 1.025 g/ml containing both lipid and protein. Acrylamide electrophoresis in 8 m urea after total delipidation demonstrated liposomal bands which coelectrophoresed with three of four very low density lipoprotein bands; there was no band corresponding to the very low density lipoprotein band which travels furthest in acrylamide electrophoregrams. However, acrylamide electrophoresis of the apoproteins of serum high density lipoprotein from orotic acid-fed animals revealed the presence of the latter band. The results indicate that liver liposomes from orotic acid-fed rats apparently contain the low density apoprotein and probably several other very low density lipoprotein peptides.
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PMID:Serum lipoprotein accumulation in the livers of orotic acid-fed rats. 436 41

The interaction of ethanol with lipid metabolism is complex. When ethanol is present, it becomes a preferred fuel for the liver and displaces fat as a source of energy. This favors fat accumulation. In addition, the altered redox state secondary to the oxidation of ethanol promotes lipogenesis, for instance, through enhanced formation of acylglycerols. The depressed oxidative capacity of the mitochondria injured by chronic alcohol feeding also contributes to the development of the fatty liver. Accumulation of fat acts as a stimulus for the secretion of lipoproteins and the development of hyperlipemia. Hyperlipemia may also be facilitated by the proliferation of the endoplasmic reticulum after chronic ethanol consumption and the associated increase of enzymes involved in the production of triglycerides and lipoproteins. The propensity to enhance lipoprotein secretion is offset, at least in part, by a decrease in microtubules and an impairment of the secretory capacity of the liver. The level of blood lipids depends on the balance between these two opposite changes: At the early stage of alcohol abuse, when liver damage is still small, hyperlipemia will prevail, whereas the opposite occurs with severe liver injury. When hyperlipemia occurs, it involves all lipoprotein classes, including high density lipoprotein (HDL). The latter have been suggested to be responsible for the lower incidence of coronary complications of moderate drinkers compared to teetotalers, but in fact, the subtype of HDL involved (HDL3) differs from the HDL2 subtype associated with protection.
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PMID:Ethanol and lipids. 638 65


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