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

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

Adenosine administration delayed the fatty liver and cell necrosis induced by carbon tetrachloride without affecting the action of the hepatotoxin on protein synthesis and liver triacylglycerol release. Adenosine produced a drastic antilipolytic effect accompanied by a decrease in the incorporation of [1-14C]palmitic acid into triacylglycerols and free fatty acids of the liver. Furthermore, a decrease in the serum levels of ketone bodies was observed at early times. The nucleoside also avoided the release of intracellular enzymes and prevented the lipid peroxidation produced by carbon tetrachloride during the 4 hr of treatment. The protective action of adenosine was transient, lasting 3-4 hr, probably the time required to be metabolized. The results suggest that the antilipolytic effect of the nucleoside, the inhibition of hepatic fatty acid metabolism, and the decrease in carbon tetrachloride-induced lipoperoxidation that it produced are involved in the delayed acute hepatotoxicity induced by carbon tetrachloride.
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PMID:Effects of adenosine on liver cell damage induced by carbon tetrachloride. 646 74

Acute fatty liver of pregnancy occurs in some women. As other cases of microvesicular steatosis are due to impaired mitochondrial oxidation of fatty acids, we investigated the effects of female sex hormones on liver mitochondria in female mice. Three hours after administration of both estradiol (36 mumol/kg) and progesterone (150 mumol/kg), the in vitro beta-oxidation of [U-14C]palmitic acid and the activity of the tricarboxylic acid cycle decreased 49 and 54%, whereas the in vivo oxidation of [U-14C]palmitic acid decreased 38%. One week of treatment with both sex hormones produced ultrastructural lesions of mitochondria, decreased the recovery of mitochondrial proteins by 34%, increased state 4 respiration by 54-77%, and decreased the activities per gram of liver of several enzymes involved in the activation, mitochondrial uptake, and oxidation of fatty acids by 34-54%. We conclude that female sex hormones have deleterious effects on liver mitochondria and suggest that these effects, together with other factors, may contribute to the development of acute fatty liver of pregnancy in some women.
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PMID:Effects of female sex hormones on mitochondria: possible role in acute fatty liver of pregnancy. 784 Jan 91

In the present work the influence of zinc deficiency on fat content and fatty acid composition of liver and fatty acid composition of brain of rats with a high food intake was investigated. Using the force-feeding technique the rats were fed 14.5 g food daily at days 1 to 4, and then 11.6 g food for later days. After 7 days the zinc-deficient animals had a fatty liver which was characterized by an increase in fat content (68%) and dry matter (23%). The amounts of lauric acid, myristic acid, myristoleic acid, palmitic acid, palmitoleic acid, and oleic acid were also increased by 100 to 200% in the liver of zinc-deficient animals, whereas the amount of arachidonic acid was decreased by 29%. The amounts of phosphatidylcholine and phosphatidylethanolamine in the liver were not changed by zinc deficiency, but the fatty acid composition of these phospholipids was changed. The liver phospholipids of zinc-deficient animals had a decreased proportion of arachidonic acid, but an increased proportion of docosahexaenoic acid. In the zinc-deficient animals there also existed a positive correlation between the fat content in the liver and the ratio between linoleic and arachidonic acid in the liver and a negative correlation between the fat content in the liver and the amount of arachidonic acid in the liver. These correlations as well as the changes in liver fatty acid composition of zinc-deficient animals suggest that the fatty liver might be the result of a disturbed metabolism of linoleic acid. In contrast, zinc deficiency did not influence the fatty acid composition of brain. This means that brain is protected against the effects of short-term zinc deficiency.
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PMID:[The effect of zinc depletion on the fat content and fatty acid composition of the liver and brain in forcibly fed rats]. 823 78

Severe impairment of the beta-oxidation of fatty acids, as a consequence of a single factor or a combination of different causes, leads to microvesicular steatosis of the liver. In an effort to understand the mechanism(s) leading to the development of acute fatty liver of pregnancy in some women, we determined the effects of pregnancy on the mitochondrial oxidation of fatty acids in mice. In vivo, the rate of oxidation of the whole fatty-acid chain length was determined by measuring the rate of exhalation of [14C]CO2 after intragastric administration of a tracer dose of [U-14C]palmitic acid. [14C]CO2 exhalation was not significantly decreased at 14 days of gestation, but it had declined by 40% at 18 days of gestation (i.e., 24 to 48 hr before delivery). The rate of first beta-oxidation cycle was assessed by measuring the rate of [14C]CO2 exhalation after administration of [1-14C]octanoic acid, [1-14C]butyric acid or [1-14C]palmitic acid. [14C]CO2 exhalation had declined by 60%, 46%, and 24% after administration of [1-14C]octanoic acid, [1-14C]butyric acid and [1-14C]palmitic acid, respectively, in 18-day-pregnant mice. Total hepatic lipids and triglycerides, expressed per gram of liver, remained unchanged in 18-day-pregnant mice. In vitro, the rate of mitochondrial beta-oxidation (expressed per milligram of protein) had decreased by 47% at 18 days' gestation with [U-14C]palmitic acid as substrate and by 33% with [1-14C]octanoic acid but remained unchanged with [1-14C]palmitic acid. The activity of the tricarboxylic acid cycle, assessed by the formation of [14C]CO2 from [1-14C]acetic acid, had decreased by 24%. We conclude that the mitochondrial oxidation of fatty acids decreased during late-term pregnancy in mice as a consequence of both decreased mitochondrial beta-oxidation of medium-chain fatty acids, and decreased activity of the tricarboxylic acid cycle. We suggest that this effect, in combination with other factors, may contribute to the development of fatty liver of pregnancy in some pregnant women.
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PMID:Decreased mitochondrial oxidation of fatty acids in pregnant mice: possible relevance to development of acute fatty liver of pregnancy. 847 67

Glucocorticoid administration may produce fatty liver in humans. We investigated the effects of dexamethasone on hepatic mitochondria and lipid metabolism in mice. Dexamethasone 21-phosphate (20 microM) did not inhibit the mitochondrial inner membrane-bound very-long-chain acyl-CoA dehydrogenase but inhibited the matrixlocated long-, medium-, and short-chain dehydrogenases. Dexamethasone 21-phosphate (20 microM) inhibited the first beta-oxidation cycle of [1-(14C)]butyric acid and [1-(14C)]octanoic acid but not that of [1-(14C)]palmitic acid. Administration of dexamethasone 21-phosphate (100 mg/kg) decreased the in vivo oxidation of [1-(14C)]butyric acid and [1-(14C)]octanoic acid into [14C]CO2 but not that of [1-(14C)]palmitic acid and decreased the hepatic secretion of triglycerides. After 5 days of treatment (100 mg/kg daily), hepatic triglycerides were increased and both microvesicular steatosis and ultrastructural mitochondrial lesions were present. In conclusion, glucocorticoids inhibit medium- and short-chain acyl-CoA dehydrogenation and hepatic lipid secretion in mice. These effects may account for their steatogenic effects in humans.
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PMID:Glucocorticoids inhibit mitochondrial matrix acyl-CoA dehydrogenases and fatty acid beta-oxidation. 917 24

The use of near-infrared reflectance spectroscopy (NIRS) on a meat product is described in this report. The aim of the study was to develop calibration equations to predict the chemical composition of goose fatty liver (foie gras) with lipid contents greater than 40% of the fresh pate. Spectra of 52 foie gras samples were collected in the visible and NIR region (400 to 2,498 nm). Calibration equations were computed for DM, CP, lipids and fatty acids using modified partial least-squares regression. R2 values were high for the total lipid content (0.805) and DM (0.908) but were low for ash (0.151) and relatively low for protein content (0.255). For the major fatty acids, R2 ranged from 0.886 for palmitic acid to 0.988 for oleic acid. Oleic acid, the main fatty acid of the liver, and the stearic acid had higher R2 values than the less represented fatty acids. This study suggests that the NIRS technique can be used to predict lipid content and the fatty acid composition of goose fatty livers, but calibration must be built on a larger number of samples to generate accurate predictions.
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PMID:The use of near-infrared reflectance spectroscopy in the prediction of the chemical composition of goose fatty liver. 1173 80

Liver fatty acid binding protein (L-FABP) has been proposed to limit the availability of long-chain fatty acids (LCFA) for oxidation and for peroxisome proliferator-activated receptor alpha (PPAR-alpha), a fatty acid binding transcription factor that determines the capacity of hepatic fatty acid oxidation. Here, we used L-FABP null mice to test this hypothesis. Under fasting conditions, this mutation reduced beta-hydroxybutyrate (BHB) plasma levels as well as BHB release and palmitic acid oxidation by isolated hepatocytes. However, the capacity for ketogenesis was not reduced: BHB plasma levels were restored by octanoate injection; BHB production and palmitic acid oxidation were normal in liver homogenates; and hepatic expression of key PPAR-alpha target (MCAD, mitochondrial HMG CoA synthase, ACO, CYP4A3) and other (CPT1, LCAD) genes of mitochondrial and extramitochondrial LCFA oxidation and ketogenesis remained at wild-type levels. During standard diet, mitochondrial HMG CoA synthase mRNA was selectively reduced in L-FABP null liver. These results suggest that under fasting conditions, hepatic L-FABP contributes to hepatic LCFA oxidation and ketogenesis by a nontranscriptional mechanism, whereas L-FABP can activate ketogenic gene expression in fed mice. Thus, the mechanisms whereby L-FABP affects fatty acid oxidation may vary with physiological condition.
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PMID:Liver fatty acid binding protein is required for high rates of hepatic fatty acid oxidation but not for the action of PPARalpha in fasting mice. 1465 98

Hepatic steatosis increases the extent of cellular injury incurred during ischemia/reperfusion (I/R) injury. (-)-Epigallocatechin gallate (EGCG), the major flavonoid component of green tea (camellia sinensis) is a potent antioxidant that inhibits fatty acid synthase (FAS) in vitro. We investigated the effects of EGCG on hepatic steatosis and markers of cellular damage at baseline and after I/R injury in ob/ob mice. Animals were pretreated with 85 mg/kg EGCG via intraperitoneal (ip) injection for 2 days or oral consumption in the drinking water for 5 days before 15 minutes of warm ischemia and 24 hours of reperfusion. After EGCG administration, total baseline hepatic fat content decreased from baseline. Palmitic acid and linoleic acid levels also were reduced substantially in all ECGC-treated animals before I/R. Alanine aminotransferase (ALT) levels decreased in all EGCG-treated animals compared with control animals after I/R. Histologic analysis demonstrated an average decrease of 65% necrosis after EGCG administration. EGCG administration also increased resting hepatic energy stores as determined by an increase in cellular adenosine triphosphate (ATP) with a concomitant decrease in uncoupling protein 2 (UCP2) before I/R. Finally, there was an increased level of glutathione (GSH) in the EGCG-treated mice compared with the vehicle-treated mice both at baseline and after I/R. In conclusion, taken together, this study demonstrates that treatment with ECGC by either oral or ip administration, significantly protects the liver after I/R, possibly by reducing hepatic fat content, increasing hepatic energy status, and functioning as an antioxidant.
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PMID:Short-term administration of (-)-epigallocatechin gallate reduces hepatic steatosis and protects against warm hepatic ischemia/reperfusion injury in steatotic mice. 1571 8

The present study was designed to define an experimental model of hepatocellular steatosis with a fat overaccumulation profile in which the metabolic and cytotoxic/apoptotic effects could be separated. This was accomplished by defining the experimental conditions of lipid exposure that lead to significant intracellular fat accumulation in the absence of overt cytotoxicity, therefore allowing to differentiate between cytotoxic and apoptotic effects. Palmitic (C16:0) and oleic (C18:1) acids are the most abundant fatty acids (FFAs) in liver triglycerides in both normal subjects and patients with nonalcoholic fatty liver disease (NAFLD). Therefore, human hepatocytes and HepG2 cells were incubated with a mixture of different proportions of saturated (palmitate) and unsaturated (oleate) FFAs to induce fat-overloading. Similar intracellular levels of lipid accumulation as in the human steatotic liver were achieved. Individual FFAs have a distinct inherent toxic potential. Fat accumulation, cytotoxicity and apoptosis in cells exposed to the FFA mixtures were investigated. The FFA mixture containing a low proportion of palmitic acid (oleate/palmitate, 2:1 ratio) is associated with minor toxic and apoptotic effects, thus representing a cellular model of steatosis that mimics benign chronic steatosis. On the other hand, a high proportion of palmitic acid (oleate/palmitate, 0:3 ratio) might represent a cellular model of steatosis in which saturated FFAs promote an acute harmful effect of fat overaccumulation in the liver. These hepatic cellular models are apparently suitable to experimentally investigate the impact of fat overaccumulation in the liver excluding other factors that could influence hepatocyte behaviour.
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PMID:A human hepatocellular in vitro model to investigate steatosis. 1718 72


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