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

The sequential pattern of lipid accumulation and associated biochemical changes were studied in two commonly used experimental models of nutritional fatty liver in rats. Female rats were maintained for 8 weeks on high fat, low protein diets containing adequate methionine and choline, and drinking water ad libitum (Diet 1), or deficient in methionine and choline and containing 20% ethanol as a substitute for drinking water (Diet 2). Histologically, there was a progressive increase in liver lipids, mainly in the periportal areas. Occasional foci of liver cell necrosis with lipogranuloma formation occurred in areas of severe fatty change. These changes appeared earlier and were more marked in rats maintained on Diet 2. Electron micrographs revealed large lipid droplets in the liver cells, which sometimes contained myelin figures. The mitochondria were enlarged, distorted and appeared as amorphous structures with disorientated cristae in rats on Diet 1, whereas they had a condensed conformation in rats maintained on Diet 2. Rough endoplasmic reticulum was fragmented and degranulated particularly in rats on Diet 1, and smooth endoplasmic reticulum showed hyperplasia and vesiculation in rats on Diet 2. There was a progressive increase in the total liver lipids and triglycerides in both the groups of rats. This fatty change was accompanied by a significant increase in hepatic 3-hydroxybutyrate, acetoacetate, malate, 2-oxoglutarate, citrate, lactate, ammonia, glutamate, alanine and aspartate, and a significant decrease in oxaloacetate, urea and glucose concentrations. The mass action ratios for alanine aminotransferase, aspartate amino transferase, and glutamate dehydrogenase, generally moved in a parallel direction. Hepatic ATP content was considerably reduced accompanied by a decrease in [ATP]/[ADP] ratios and a significant increased in [lactate]/[pyruvate] and [3-hydroxybutyrate]/[acetoacetate] ratios. There was a corresponding decrease in the [NAD+]/[NADH] ratios both in the cytoplasmic and mitochondrial compartments. These biochemical changes were particularly severe in rats maintained on Diet 1 and Diet 2 for 8 weeks. There was a very good relationship between impaired mitochondrial and endoplasmic reticulum functions, redox and phosphorylation states, and the relevance of their changes to the fate of fatty liver cells.
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PMID:Lipid accumulation in the rat liver: a histological and biochemical study. 23

Induction of hepatic steatosis and suppression of hepatic ATP levels, protein synthesis and gluconeogenesis subsequent to administration of ethionine may be consequences of interference by this compound with mitochondrial phosphorylation of ADP. The mitochondrial dysfunction is not a direct action of ethionine on the organelle.
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PMID:Depression by ethionine of phosphorylating oxidation in hepatic mitochondria. 65 30

1. The changes in a number of metabolic measurements brought about by low-biotin diets associated with high and low incidences of fatty liver and kidney syndrome (FLKS) were studied in healthy 4-week-old broiler chicks. 2. Liver pyruvate carboxylase (pyruvate: CO2 ligase (ADP); EC 6.4.1.1) activity was low in birds fed on a diet causing a high incidence FLKS but the addition of fat or protein to this diet, to decrease the incidence of FLKS, increased enzyme activity. 3. Liver weights, blood lactate concentrations, plasma lactate dehydrogenase (L-lactate: NAD oxidoreductase; EC 1.1.1.27) activitvities and values for C16:1 : C18:0 fatty acid in liver, adipose tissue and plasma triglyceride were highest in birds fed on the high-FLKS diet and all measurements were negatively correlated with pyruvate carboxylase activity. 4. Birds with high plasma lactate dehydrogenase activity or triglyceride C16:1 : C18:0 values were the most likely to develop FLKS when fasted. 5. There was no evidence that increased liver weight was associated with increase activities of certain other liver enzymes. 6. It is concluded that FLKS occurs in birds with little or no hepatic gluconeogenic capacity via pyruvate carboxylase as a result of a dietary insufficiency of biotin but that the initiation of the syndrome in probably associated with the inhibition of other pathways of gluconeogenesis.
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PMID:Metabolic changes associated with the occurrence of fatty liver and kidney syndrome in chicks. 69 61

Rats fed ethanol (36% of total calories in a nutritionally adequate liquid diet) for 5 weeks develop functional alterations of hepatic mitochondria and steatosis of the liver. At the fatty liver stage, ADP-stimulated respiration of mitochondria was depressed in ethanol fed rats by 30% (p less than 0.001) with glutamate + malate and by 23% (p less than 0.001) with succinate as substrates. A similar decrease was noted in the respiratory control ratio (RCR) (34% and 29%, respectively). The total lipid content of the liver increased 2.6 fold (p less than 0.001). Mitochondrial dysfunction could be prevented, in part, by the treatment with a synthetic derivative of prostaglandin E1, misoprostol, at a mean daily dose of 80 micrograms/kg of body weight. The RCR with glutamate + malate as substrates was improved by 36% (p less than 0.05). We conclude that misoprostol attenuates several functional alterations in liver mitochondria during alcohol feeding.
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PMID:The effect of the prostaglandin analogue-misoprostol on rat liver mitochondria after chronic alcohol feeding. 190 12

Collagen-, arachidonate- and ADP-stimulated platelet thromboxane B2 (TXB2) formation was studied in platelet-rich plasma (PRP) of 14 alcoholics, 7 of whom had a biopsy-verified alcoholic fatty liver. On admission for detoxication, the alcoholics showed decreased platelet count and aggregability (p less than 0.001) as compared to nonalcoholic healthy controls. Platelet TXB2 formation was decreased (p less than 0.01), if PRP was stimulated by arachidonate, but not if it was stimulated by ADP or collagen. In contrast, 9-14 days after ethanol withdrawal platelet TXB2 formation had increased to markedly higher levels than those seen in nonalcoholic controls (p less than 0.01), if PRP was stimulated by ADP, but not if it was stimulated by arachidonate or collagen. Skin bleeding time was found to be prolonged (p less than 0.05) on admission in alcoholics having fatty liver, but it normalized within 2 weeks after ethanol withdrawal. We conclude that the effect of ethanol withdrawal in alcoholics on platelet TXB2 formation is influenced by platelet count, aggregability and the agonist used to induce platelet aggregation.
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PMID:Platelet thromboxane formation capacity after ethanol withdrawal in chronic alcoholics. 314 Dec 51

Four Macaca fascicularis monkeys were maintained 1 year on a liquid diet containing 26% of calories as ethanol. Four control animals were fed a liquid diet of equivalent calories with protein, carbohydrate, and fat being substituted for ethanol calories. In liver mitochondria prepared from ethanol-fed monkeys (ethanol mitochondria), respiratory control was lowered 20% due to a decrease in state 3 respiration (28%). This was also accompanied by a 20% decrease in ADP translocation into ethanol mitochondria. The major change was a 61% decrease in cytochrome oxidase activity. The respiratory rate in the presence of uncoupler was also lowered 14%, but the decrease was not statistically significant. In contrast with our earlier observations with Macaca nemestrina, no significant ethanol-induced changes were observed in enzyme activities associated with the microsomal electron transport system, and no ethanol-elicited fatty liver was evident. The major changes in fatty acid composition of microsomal and mitochondrial phospholipids were increased amounts of palmitoleic and oleic acids, and decreased amounts of linoleic and arachidonic acids.
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PMID:Ethanol-related changes in liver microsomes and mitochondria from the monkey, Macaca fascicularis. 641 31

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.
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PMID:Biochemical and morphological alterations of baboon hepatic mitochondria after chronic ethanol consumption. 653 46

Male rats developed fatty liver after being fed on an ethanol-containing diet for 31 days. Liver mitochondria from these animals catalysed ATP synthesis at a slower rate when compared with mitochondria from pair-fed control rats (control mitochondria), and demonstrated lowered respiratory control with succinate as substrate, owing to a decrease in the State-3 respiratory rate. Respiration in the presence of uncoupler was comparable in mitochondria from both groups of rats. Translocation of both ATP and ADP was decreased in mitochondria from ethanol-fed rats, with ADP uptake being lowered more dramatically by ethanol feeding. Parameters influencing adenine nucleotide translocation were investigated in mitochondria from ethanol-fed rats. Experiments performed suggested that lowered adenine nucleotide translocation in these mitochondria is not the result of inhibition of the translocase by either long-chain acyl-CoA derivatives or unesterified fatty acids. Analysis of endogenous adenine nucleotides in these mitochondria revealed lowered ATP concentrations, but no decrease in total adenine nucleotides. In experiments where the endogenous ATP in these mitochondria was shifted to higher concentrations by incubation with oxidizable substrates or defatted bovine serum albumin, the rate of ADP translocation was increased, with a linear correlation being observed between endogenous ATP concentrations and the rate of ADP translocation. The depressed ATP concentration in mitochondria from ethanol-fed rats suggests that the ATP synthetase complex is replenishing endogenous ATP at a slower rate. The lowered ATPase activity of the ATP synthetase observed in submitochondrial particles from ethanol-fed animals suggests a decrease in the function of the synthetase complex. A decrease in the rate of ATP synthesis in mitochondria from ethanol-fed rats is sufficient to explain the decreased ADP translocation and State-3 respiration.
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PMID:Control of adenine nucleotide metabolism in hepatic mitochondria from rats with ethanol-induced fatty liver. 709 25

Male rats developed fatty liver after being fed an ethanol-containing diet for 31 days. Liver mitochondria from these animals (ethanol mitochondria) catalyzed ATP synthesis at a slower rate than did mitochondria from pair-fed control rats (control mitochondria). Furthermore, ATP translocation was decreased in ethanol mitochondria and parameters influencing such were investigated. Several experiments indicated that ADP uptake into ethanol mitochondria is not decreased due to inhibition of the adenine nucleotide translocase by either long chain acyl CoA derivatives or unesterified fatty acids. Analyses of endogenous adenine nucleotides in ethanol mitochondria revealed lower ATP concentrations, but no decrease in total adenine nucleotides. In experiments where endogenous ATP was shifted to higher concentrations by incubation with BSA, the rate of ADP translocation was increased, with a linear correlation being observed between endogenous ATP concentrations and the rate of ADP translocation. The depressed ATP concentration in ethanol mitochondria suggests that the ATP synthetase complex is replenishing endogenous ATP at a slower rate. A decrease in the rate of ATP synthesis in ethanol mitochondria is sufficient to explain the decreased ADP translocation.
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PMID:Control of adenine nucleotide translocation in liver mitochondria from ethanol-fed rats. 724 34

Nicotinamide (NIC) is known to increase the synthesis of pyridine nucleotides and also to inhibit the hydrolysis of them to ADP-ribose, which in turn is involved in Ca2+ release from mitochondria via the ADP ribosylation of crucial mitochondrial proteins. In this work, we test the potential ability of NIC to be a late protective agent against CCl4-induced liver necrosis. We observed that 1 g/kg po NIC, 30 min before or 6 or 10 hr after CCl4 (1 ml/kg), given ip as a 20% (v/v) solution in olive oil, was able to significantly prevent the necrogenic effect of the hepatotoxin at 24 hr as evidenced by determination of isocitric dehydrogenase activity in plasma or by histological observation. NIC administration 6 hr after CCl4 prevented fatty liver induced by hepatotoxin at 24 hr. NIC did not modify CCl4-induced lipid peroxidation process at 1 hr after CCl4 and decreased the covalent binding of 14CCl4 to lipids. NIC decreased the levels of 14CCl4 reaching the liver when given 30 min before hepatotoxin but not when given 6 hr after it. NIC lowered body temperature of rats at 1, 3, and 6 hr and augmented it at 24 hr after CCl4. NIC concentrations in liver as determined by GC/MS/SIM analysis were 21 micrograms/g liver 1 hr after administration and 53 micrograms/g at 3 hr. Late preventive effects of NIC against CCl4 induced liver necrosis when given at 6 or 10 hr after CCl4 are compatible with the hypothesis that NIC restores mitochondrial ability for Ca2+ uptake. This hypothesis remains to be proved and is being further challenged in our laboratory.
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PMID:Nicotinamide late protective effects against carbon tetrachloride-induced liver necrosis. 795 79


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