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

Splanchnic metabolism was studied to quantify changes underlying the fatty liver, hyperlipemia, and hypoglycemia produced by ethanol. Four subjects fasted for 15 h were compared with five subjects fasted for 69 h under basal conditions and during continuous intravenous infusion of sufficient ethanol to give a concentration of 3-5 mM in arterial blood plasma. Splanchnic storage of fatty acids was estimated from the difference between uptake of FFA and secretion of derived products. Basal values for splanchnic uptake of FFA were twofold higher after the 69-h fast while splanchnic storage of fatty acids and production of ketone bodies increased threefold. Values for basal secreation into the blood of triglycerides derived from FFA were similar in the two groups. In both nutritional states, the fraction of FFA taken up in the splanchnic region oxidized to ketone bodies and to CO2 fell when ethanol was given because of preferential oxidation of ethanol to acetate, and the fraction esterified rose. However, systemic transport and splanchnic uptake of FFA fell with ethanol in subjects fasted 15 h, so that neither storage of triglycerides in splanchnic tissues nor secretion into the blood increased. In subjects fasted 69 h, ethanol increased transport of FFA and splanchnic storage of fat. In all but one subject it also increased secretion of triglycerides into the blood. The concentration of glucose in blood fell during ethanol infusion in all five subjects undergoing the 69-h fast. Mean splanchnic glucose production was maintained at about one-half of the pre-ethanol value, despite virtual cessation of splanchnic uptake of lactate and of those amino acids that are metabolized via malate. Quantitative estimates of extrasplanchnic metabolism suggest that enhanced formation of alpha-glycerophosphate from glucose, in addition to impaired hepatic gluconeogenesis, may contribute to ethanol-induced hypoglycemia in man.
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PMID:Effects of a 3-day fast and of ethanol on splanchnic metabolism of FFA, amino acids, and carbohydrates in healthy young men. 17 79

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

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.
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PMID:Effect of chronic ethanol ingestion on fatty acid oxidation by hepatic mitochondria. 117 Oct 98

Previous research has shown that a combination of feed restriction and dietary 1,3-butanediol starting at 14 d post-partum resulted in fatty liver and ketosis. Sixteen multiparous Holstein cows were used to determine effects of feed restriction or 1,3-butanediol as separate treatments. Treatments during d 14 to 42 postpartum were 1) control (ad libitum intake), 2) 20% feed restriction, or 3) control plus dietary 1,3-butanediol (5.5% of DM). From d 43 to 56, cows assigned to treatments 2 and 3 received a combination of feed restriction and butanediol. One cow on treatment 2 developed ketosis, but not fatty liver, after only 4 d of feed restriction. No other cows developed fatty liver or ketosis. Both treatments decreased milk production compared with controls. Feed restriction increased the extent of negative energy balance and caused transient increases in concentrations of NEFA, acetate, and beta-hydroxybutyrate in plasma. Concentrations of beta-hydroxybutyrate and insulin in plasma were increased by butanediol, which is a potent ketone body precursor. Concentration of glycogen in liver was less in feed-restricted cows, whereas glycogen and total lipid were greater in cows given butanediol separately. Gluconeogenic capacity of liver slices was not different among groups. Addition of 1,3-butanediol to in vitro incubation media decreased oxidation of propionate to CO2. Neither feed restriction nor dietary 1,3-butanediol as separate treatments induced the fatty liver and ketosis observed in earlier experiments in which the two treatments were given together.
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PMID:Metabolic changes in blood and liver of dairy cows during either feed restriction or administration of 1,3-butanediol. 178 95

Peritoneal dialysis is a relatively safe and effective form of therapy for acute renal failure (ARF). As dextrose in the dialysate provides the osmotic gradient to achieve fluid removal, frequent exchanges with dialysate containing high dextrose is occasionally used to achieve negative balance in fluid overloaded patients. It has previously been shown that dextrose absorption from the peritoneal cavity is significant. Using indirect calorimetry and analyzing the dialysate effluent for its dextrose concentration, we studied the effects of high dextrose-containing dialysate in five patients with ARF. Despite minimal intake of calories, all patients had an RQ greater than 1.0 consistent with net lipogenesis resulting from dextrose absorbed from the peritoneal cavity. Four of five patients absorbed greater than 500 g of dextrose over 24 h. As overfeeding could lead to hepatic steatosis, increased CO2 production with worsening of respiratory failure, and hyperglycemia, the risks of using high dextrose-containing dialysate fluids should be weighed carefully against potential benefits. When nutritional support is indicated in such patients, contribution of dextrose calories from dialysate fluid should be taken into account.
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PMID:Peritoneal dialysis for acute renal failure: overfeeding resulting from dextrose absorbed during dialysis. 210 81

The effects of ethanol administration on activity and regulation of carnitine palmitoyltransferase I (CPT-I) were studied in hepatocytes isolated from rats fed a liquid, high-fat diet containing 36% of total calories as ethanol or an isocaloric amount of sucrose. Cells were isolated at several time points in the course of a 5-week experimental period. Ethanol consumption markedly decreased CPT-I activity and increased enzyme sensitivity to inhibition by exogenously added malonyl-CoA. Changes in enzyme activity occurred sooner than those in enzyme sensitivity. Fatty acid oxidation to CO2 and ketone bodies was depressed in hepatocytes from ethanol-fed animals during the first part of the treatment. At the end of the 35-day period, there were no longer differences in the rate of ketogenesis between the two groups. At that time, however, the rate of CO2 formation was still impaired in the ethanol-fed animals. Furthermore, addition of ethanol or acetaldehyde to the incubation medium strongly depressed CPT-I activity and rates of fatty acid oxidation in hepatocytes from ethanol-treated rats, whereas these effects were much less pronounced in cells from control animals. The response of CPT-I activity to insulin, glucagon, vasopressin, and phorbol ester was blunted in cells derived from ethanol-fed rats. These changes in the regulation of CPT-I activity corresponded with those observed in the rate of fatty acid oxidation. It is concluded that CPT-I may play a role in the generation of the ethanol-induced fatty liver.
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PMID:Effects of ethanol feeding on the activity and regulation of hepatic carnitine palmitoyltransferase I. 306 12

A micro-technique was developed to measure fatty acid oxidation in vitro and to investigate its possible derangement in alcoholic fatty liver disease. Percutaneous liver biopsy specimens were obtained from nine control subjects and 28 alcoholic patients with mild to severe fatty liver. Fresh tissue (10-15 mg) was incubated at 37 degrees C for 90 min in a sealed reaction flask containing 1.92 mmol/l [1-14C]palmitic acid (1-2 microCi) and 1% essentially fatty acid free albumin in Krebs-Henseleit buffer, pH 7.4. Radiolabelled CO2 and perchloric acid-soluble ketone bodies were isolated and counted. CO2 production was markedly reduced in alcoholic patients with mild and severe fatty liver compared with controls. This depression was reversed by the addition of malate to the reaction flask but not by carnitine or coenzyme A. Ketone body production was similar in controls and patients with mild and severe fatty liver. After the incubation in vitro, the tissue was extracted with chloroform/methanol and the triglyceride fraction isolated by thin layer chromatography and counted for radioactivity. The rate of palmitic acid incorporation into triglyceride was higher in alcoholic patients, particularly those with severe fatty infiltration, compared with controls. It is suggested that alcoholic fatty liver is accompanied by a progressive reduction in palmitic acid oxidation with the major defect occurring in the tricarboxylic acid cycle. In contrast, the rate of palmitic acid esterification into triglyceride is enhanced.
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PMID:Palmitic acid oxidation and incorporation into triglyceride by needle liver biopsy specimens from control subjects and patients with alcoholic fatty liver disease. 309 34

The concentrations of malonyl-CoA, citrate, ketone bodies and long-chain acylcarnitine were measured in freeze-clamped liver samples from fed or starved normal, partially hepatectomized or sham-operated rats. These parameters were used in conjunction with measurements of the concentration of plasma non-esterified fatty acids and the rates of hepatic lipogenesis to obtain correlations between rates of fatty acid delivery to the liver, lipogenesis and fatty acid oxidation to ketone bodies and CO2. These correlations indicated that the development of fatty liver after partial hepatectomy is due to an increased partitioning of long-chain acyl-CoA towards acylglycerol synthesis and away from acylcarnitine formation. However, this did not appear to be due to an altered relationship between hepatic malonyl-CoA concentration and acylcarnitine formation. For any concentration of long-chain acylcarnitine, the concentrations of both hepatic and blood ketone bodies were significantly lower in partially hepatectomized rats than in normal or sham-operated animals. This indicated that a lower proportion of the product of beta-oxidation was used for ketone-body formation and more for citrate synthesis in the regenerating liver, especially during the first 24 h after resection. This inference was supported by the changes in hepatic citrate concentrations observed. The high rates of lipogenesis that occurred in the liver remnant were accompanied by an altered relationship between lipogenic rate and hepatic malonyl-CoA concentration, such that much lower concentrations of malonyl-CoA were associated with any given rate of lipogenesis. These adaptations are discussed in relation to the requirements by the remnant for high rates of energy formation through the tricarboxylic acid cycle during the first 24 h after resection, and the possibility that cycling between fatty acid oxidation and synthesis may occur to a greater degree in regenerating liver.
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PMID:Altered interactions between lipogenesis and fatty acid oxidation in regenerating rat liver. 359 2

In 16 healthy volunteers and in 39 patients with liver diseases (fatty liver, chronic persistent and chronic active hepatitis, hepatic cirrhosis) a simplified aminopyrine breath test (ABT) was carried out using a "tracer" dose of 3 mg (111 kBq) 14C-aminopyrine. The exhaled 14CO2 measured 1 h after intake amounted to values between 771 and 1337 DPM/mmol CO2/70 kg body weight in healthy controls. The amount of exhaled 14CO2 decreased in the order: fatty liver greater than chronic, active hepatitis greater than active, compensated cirrhosis greater than active, decompensated cirrhosis. Between the values of ABT and various conventional laboratory liver tests (alanine-aminotransferase, alanine-aminopeptidase, aspartate-aminotransferase, gamma-glutamyltransferase, total serum bilirubin) significant correlations were found (r = 0.6019 to 0.7765, n = 55; p less than 0.001). The proposed modification of the breath test is of advantage in that it requires a very low dose of aminopyrine and is easily practicable.
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PMID:A simple method for routine determination of the metabolic liver capacity: the aminopyrine breath test. 392 2

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


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