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)

In order to clarify the mechanism of alcoholic fatty liver, rats were reared with alcohol diet from adult, foetal or weanling periods. When rats were fed with the diet from adult for 4 weeks, these livers showed apparent fatty deposition histologically and biochemically. Low density lipoprotein (LDL) in serums of these rats lowered in level significantly than control, which indicate decreased production of secretion of very low density lipoprotein (VLDL) in the liver from which converted to LDL in peripheral tissues. When rats were reared with the diet from their foetal life, their livers deposited little of fat at any time examined after birth up to 13 weeks in spite of good diet uptake. The same phenomenon was observed in rats reared from their weanling period with the diet. In situ liver perfusion was performed to clarify the anti-fatty liver mechanism. Ketone body (KB) production rates from palmitate infused constantly at physiological concentration and bile production rates were not different among control, weanling and foetal groups. Oxygen consumption rate in control decreased after infusion of palmitate-albumin complex solution. However the rates in weanling and foetal alcohol rats increased significantly after infusion of the solution. The latter group showed more increase in rate than the former. When theoretical oxygen consumption for production of KB was compared with actual one, livers from control rats seemed to use the whole oxygen for KB production. On the other hand only 59.7% of whole oxygen in foetal alcohol group and 85.9% in weanling group used for KB production respectively. It is surmized that the increased non ketone oxygen in these groups, especially in foetal alcohol group, indicate the anti-fatty liver mechanism in these groups, probably augmented FFA oxidation. Electrophoretic analysis of lipoproteins in chronic alcoholisms showed decreased beta and pre-beta band and increased alpha band. These changes returned to normal after 1 week of admission. These experimental and clinical data indicate that impaired oxidation of FFA is an important factor for the formation of alcoholic fatty liver and impaired transport of fat from liver might enhance the change in the liver.
 ...
PMID:[Experimental and clinical studies on the mechanism of alcoholic fatty liver (author's transl)]. 54 10

To study possible factors in the pathogenesis of the ethanol-induced fatty liver, we investigated the effect of chronic ethanol consumption on the metabolism of fatty acids by isolated hepatic mitochondria. Chronic ethanol consumption resulted in decreased fatty acid oxidation, as evidenced by a reduction in oxygen uptake and CO2 production associated with the oxidation of fatty acids. The State 3 rate of oxygen uptake was depressed to a greater extent than the State 4 or the uncoupler-stimulated rate; the respiratory control ratio was also decreased. Therefore, one site of action of chronic ethanol feeding is on oxidative phosphorylation. The reduction in fatty acid oxidation, in general, is not due to an effect on the activation or translocation of fatty acids into the mitochondria. There was no effect by ethanol feeding on the activity of palmitoyl coenzyme A synthetase, whereas carnitine palmitoyltransferase activity was increased. The use of an artificial system (formazan production) to study beta oxidation in the absence of the electron transport chain is described. In the presence of fluorocitrate, which inhibits citric acid cycle activity, ketogenesis and formazan production were increased by chronic ethanol consumption. Thus beta oxidation to the level of acetyl-CoA is not impaired by chronic ethanol consumption. Total oxidation of fatty acids to CO2 is depressed by chronic ethanol intoxication because of effects on oxidative phosphorylation or the citric acid cycle (or both). Neither nutritional deficiency, cofactor depletion, nor the presence of ethanol in vitro explains these effects. Several of the effects of chronic ethanol consumption on fatty acid oxidation are mimicked by acetaldehyde and acetate, products of ethanol oxidation. Chronic ethanol consumption leads to persistent impairment of mitochondrial oxidation of fatty acids to CO2. However, oxidation of fatty acids to acetyl-CoA is not decreased by chronic ethanol consumption.
 ...
PMID:Effect of chronic ethanol ingestion on fatty acid oxidation by hepatic mitochondria. 117 Oct 98

Excessive consumption of ethanol results in reversible redox changes in the liver that are mainly responsible for the accumulation of triglycerides and the fatty liver of the alcoholic patient. In spite of continuing alcohol abuse, only a fraction of all alcoholics will develop alcoholic hepatitis and eventually cirrhosis. Genetic predisposition and environmental factors (in particular the often poor nutrition of the alcoholic) probably play an important role in the evolution of these complications. The generation of reactive oxygen species increases during the metabolism of ethanol, but their pathogenetic role in alcoholic liver disease in man is not clear. Acetaldehyde, a metabolite of ethanol, can react with proteins and form stable adducts. Such neoantigens may elicit an immunologic response which could in part be responsible for the liver cell damage associated with excessive alcohol consumption. Since no satisfactory animal model for alcoholic liver disease exists, the relative importance of the various factors involved in alcoholic liver disease is difficult to assess.
 ...
PMID:[Pathogenesis of alcoholic liver disease]. 158 33

In order to elucidate active oxygen in liver diseases, activities, electrophoretic profiles and immunolocalization of superoxide dismutase (SOD) in human liver specimens were investigated. Activities and electrophoresis were studied using liver homogenates in 41 cases and immunolocalization of Cu, Zn SOD was observed in 87 cases. Total SOD activity in acute viral hepatitis (AVH) and fatty liver (FL) groups was significantly lower than that in non-specific reactive hepatitis (NSRH) group. Cu, Zn SOD activity in AVH, FL and chronic active hepatitis (CAH) groups was also significantly lower than that in NSRH group. However, no difference of Mn SOD activity, was found between NSRH group and others. Decreased activity of superoxide dismutase in liver tissues suggests the release of this enzyme from the injured hepatocytes. In electrophoretic patterns of superoxide dismutase, 3 bands of Cu, Zn SOD isozymes and 8 to 10 bands of Mn SOD isozymes were recognized. Immunocytochemical investigation revealed the localization of Cu, Zn SOD in the cytoplasm of hepatocytes. Two different distribution of Cu, Zn SOD was observed in the lobules: a diffuse localization pattern and a focal one. The latter was found in the cases of liver diseases with severe parenchymal lesion. These findings suggest that superoxide radical anion and its scavenger, superoxide dismutase, may play an important role in the pathogenesis of liver cell necrosis.
 ...
PMID:Activities, electrophoretic profiles and immunolocalization of superoxide dismutase in human liver specimens. 336 38

The purpose of this study was to determine the differences in hepatic circulation and oxygen consumption in two groups: those with nonalcoholic obesity-related fatty live and those with alcoholic fatty liver. Although the histological degree of fatty infiltration was equal in the two groups, the delta Er569-650, as an index of the regional liver blood flow estimated by spectrophotometric method, was significantly lower in alcoholic fatty liver than in nonalcoholic fatty liver, and the in vivo hepatic oxygen consumption (VO2), also determined by hepatic reflectance spectrophotometry during peritoneoscopy, tended to be lower in alcoholic fatty liver than in nonalcoholic fatty liver. The oxygen saturation of hemoglobin in local liver blood (SO2) was, however, significantly higher in alcoholic fatty liver than in nonalcoholic fatty liver. These results suggest that an increase in oxygen extraction to maintain oxygen consumption, which was indicated by the lowering of the SO2, was not found in alcoholic fatty liver, in spite of a reduction of oxygen supply to the liver. It is concluded that the impairment of hepatic circulation and hepatic oxygen consumption was more serious in alcoholic fatty liver than in nonalcoholic fatty liver, possibly contributing to a different prognosis for the two forms of fatty liver.
 ...
PMID:Hepatic circulation and hepatic oxygen consumption in alcoholic and nonalcoholic fatty liver. 339 87

Utilization of [1-14C] oleate by freshly isolated rat and goat hepatocytes was compared. Intracellular [14C] triglyceride accumulation by hepatocytes did not differ between species. At 2 h of incubation, rat hepatocytes secreted approximately 25 times more [14C] triglyceride than goat hepatocytes. Very low density lipoprotein secretion was greatest by hepatocytes incubated in media containing 4:1 oleate:bovine serum albumin. Rat hepatocytes converted three to four times more [1-14C] oleate to 14CO2 and acid-soluble products than goat hepatocytes. Rate of 14CO2 formation by both rat and goat hepatocytes increased as incubation time increased and as rate of cellular triglyceride accumulation decreased. The ratio of 14CO2:[14C] acid-soluble products formed was greater for rat than goat hepatocytes, which indicated rat hepatocytes may oxidize fatty acid more completely. Differences in metabolic rate, based on oxygen consumption, between isolated goat and rat hepatocytes were minor and could not account for marked differences in very low density lipoprotein secretion. Goat hepatocytes did not incorporate detectable quantities of labeled fatty acid into low or high density lipoproteins. Ruminants may be susceptible to fatty liver when the liver takes up large amount of nonesterified fatty acid due to an inability to efficiently export fatty acid as very low density lipoprotein triglyceride.
 ...
PMID:Triglyceride accumulation and very low density lipoprotein secretion by rat and goat hepatocytes in vitro. 341 Sep 90

Trimethyltin (TMT) is a potent neuronotoxiciant but there is little data regarding its systemic effects. In this study, female BALB/c mice were administered either 0.9% saline or 2.75 mg TMT/kg intraperitoneally (i.p.). The animals were then housed in room air or in glass chambers flushed with either 10%, 40%, or 100% oxygen. Mice were sacrificed at 4, 8, 24, and 48 h after treatment and adrenals analyzed for various neurotransmitters by ion-pairing HPLC with electrochemical detection. In addition, adrenal S-adenosylmethionine (SAM) and blood ketone bodies were determined Sections of adrenals were evaluated by electron microscopy for histopathological changes. In vivo treatment with the toxicant resulted in a significant decrease in adrenal epinephrine and norepinephrine levels as early as 8 h following treatment. This effect preceded the appearance of both clinical signs and histopathological changes in the hippocampus by 12-24 h. With exposure to TMT in room air, mouse adrenal content of epinephrine fell from 1861.3 +/- 97.3 ng/4 mg to 1493.3 +/- 137.0 ng/4 mg while norepinephrine levels fell from 779.6 +/- 32.3 ng/4 mg to 503.4 +/- 44.3 ng/4 after 8 h. Supplementation with 40% oxygen did not attenuate this effect but in the case of mice treated with TMT and housed in 100% oxygen for 48 h, actually exacerbated the adrenal epinephrine depletion. Housing in approximately half normal atmospheric oxygen (10%) neither prevented nor enhanced the effects of TMT. The epinephrine/norepinephrine ratios were: control, 2.44; TMT (room air), 1.56; TMT (10% O2), 1.72; TMT (40% O2), 1.44; TMT (100% O2), 1.07. None of the conditions used in this study caused a decrease in adrenal dopamine, 5-hydroxyindole acetic acid (5-HIAA), 5-hydroxytryptamine (5-HT) or in the level of SAM. TMT treatment significantly increased blood ketone bodies indicating additional metabolic dysfunction. The significance of these findings in relation to TMT neuronotoxicity and fatty liver syndrome are discussed.
 ...
PMID:Trimethyltin as a selective adrenal chemosympatholytic agent in vivo: effect precedes both clinical and histopathological evidence of toxicity. 372 95

We have developed a microscopic analyzing system for studying in vivo hepatic microcirculation, and measured the sinusoidal erythrocyte flow velocity simultaneously in the various sinusoids. With this system and organ reflectance spectrophotometry, the pathophysiological role of microcirculation and of energy metabolism in Zucker fatty rats were studied. The results were as follows: The erythrocyte flow velocity in the predominant sinusoids in the fatty rats was similar to that of the control rats, but the intersinusoidal erythrocyte flow was undetected in the fatty liver. Index of regional hepatic blood volume, regional hepatic blood flow and oxygen saturation of Hb decreased significantly in the fatty rats. The estimated in vivo oxygen consumption was not changed in the fatty liver. From these data, it is concluded that in Zucker fatty rats a marked fatty infiltration causes a decreased hepatic tissue blood flow and volume, but relatively homogeneous erythrocyte flow with an increased extraction of oxygen compensated the decreased vascular beds and maintained normal energy metabolism.
 ...
PMID:Hepatic microcirculation in Zucker fatty rats. 379 39

The chemiluminescence level and superoxide dismutase (SOD) activity were determined in the plasma of patients with alcoholic and non-alcoholic liver injuries. Chemiluminescence level was significantly higher in alcoholics than in non-alcoholics. It increased significantly in patients with fatty livers and had a tendency to increase with the progression of alcoholic liver injury from a fatty liver to liver cirrhosis. Mn-SOD activity was elevated in patients with alcoholic liver injuries. Furthermore, there was a positive correlation between the levels of plasma chemiluminescence and plasma Mn-SOD activity. The increases in chemiluminescence and Mn-SOD activity suggests that the generation of a large amount of activated oxygen is associated with the pathogenesis and progression of alcoholic liver injury in humans.
 ...
PMID:Chemiluminescence and superoxide dismutase in the plasma in patients with alcoholic and non-alcoholic liver injuries. 402 67

1. The influence of ethanol on the metabolism of perfused livers from normal rats and rats in various stages of development of dietary cirrhosis was studied. A choline-deficient, low-protein and high-fat diet was used. Results were obtained on oxygen consumption and carbon dioxide production, on glucose release and uptake by the liver and on changes in the concentrations of lactate and pyruvate and of beta-hydroxybutyrate and acetoacetate in the perfusion medium. 2. Oxygen consumption and carbon dioxide production were lower in fatty and cirrhotic livers than in normal livers. Ethanol had no effect on the oxygen consumption of any of the various livers. After addition of ethanol to the perfusion medium carbon dioxide production ceased almost completely in normal livers. Only a slight decrease in the carbon dioxide production occurred in fatty and cirrhotic livers. 3. With every type of liver glucose was released from the liver into the perfusion medium during the initial control period. This release continued after the addition of ethanol to the perfusion medium in experiments with normal and fatty livers, whereas with cirrhotic livers a marked uptake of glucose from the medium was found. A simultaneous release of the glycolytic end products lactate and pyruvate into the medium occurred. 4. The production of ketone bodies was equal in normal and early fatty livers (6 weeks on the fat diet). It was smaller in late fatty livers (3-4 months on the fatty diet) and in cirrhotic livers. 5. The lactate/pyruvate concentration ratio in the perfusion medium increased from 11 to 67 with normal livers, from 12 to 16 with early fatty livers, from 13 to 26 with late fatty livers and from 21 to 55 with cirrhotic livers when the livers were perfused with a medium containing ethanol. The beta-hydroxybutyrate/acetoacetate concentration ratio increased from 1.2 to 8.4 in normal livers, from 2.0 to 2.8 in early fatty livers, from 1.2 to 2.4 in late fatty livers and from 2.1 to 4.0 in cirrhotic livers when ethanol was added to the medium. 6. The effects of ethanol on liver metabolism during the development of dietary cirrhosis are discussed and related to human fatty liver and cirrhosis during chronic ethanol consumption.
 ...
PMID:Influence of ethanol on the metabolism of perfused normal, fatty and cirrhotic rat livers. 596 89


1 2 3 4 5 6 7 8 9 10 Next >>