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)

To determine whether the estrogen-induced hyperlipidemia is affected by fasting, male growing chicks were administered subcutaneously a single dose of 17 beta-estradiol (25 mg/kg body wt), and the hormone treatment lasted for 2 days with or without feed (Experiment 1). In the second experiment, chicks were initially fasted for 1 or 3 days, and then treated with the same dosage of 17 beta-estradiol as in Experiment 1 for 2 days without feed. Plasma and liver lipids, and the activities of hepatic malic enzyme, glucose-6-phosphate dehydrogenase, and hormone-sensitive lipase in the adipose tissue were determined. Compared with fed control chicks, estrogen treatment in fed birds resulted in a marked elevation of plasma lipids, especially triglyceride during the 2-day period (137 vs 2263 mg/dl). In fasted chicks, the present finding that estrogen also induced a marked hyperlipidemia is noteworthy. Upon estrogen treatment (Experiment 1), the level of plasma triglyceride in fasted birds increased about 16 times over that of the fasted control group (133 vs 2093 mg/dl). Even in chicks fasted for 5 days (Experiment 2), estrogen treatment resulted in a persistent hypertriglyceridemia (75 vs 1369 mg/dl). In fed chicks, estrogen treatment also induced a fatty liver with massive accumulation of triglyceride, but the liver of estrogen-treated/fasted chicks appeared to be normal. In both fed and fasted chicks, malic enzyme was found to be the major NADPH producing enzyme in the liver. Upon fasting, both malic enzyme and glucose-6-phosphate dehydrogenase activities decreased significantly (P less than 0.05). In fed chicks, the total activities of both enzymes increased with estrogen treatment, whereas the effect of hormone on these enzymes was less obvious in fasted chicks. The hormone-sensitive lipase activity in the adipose tissue was much lower in fed chicks compared with that of fasted birds (0.15 vs 0.33 nmol of oleic acid released/min/mg protein). Estrogen treatment in fed chicks had no effect on the hormone-sensitive lipase activity, but its activity was enhanced by the hormone treatment in fasted chicks. The present finding that hyperlipidemia persisted in estrogenized chicks during the fasting seems to indicate the complex nature of this hormonal influence on lipid metabolism.
 ...
PMID:Estrogen induces hyperlipidemia in fasted chicks. 230 May 91

We evaluated the effects of phenobarbital, an inducer, on plasma glucose and serum immunoreactive insulin levels and on hepatic glucose and drug metabolism using an animal model of non-insulin dependent diabetes mellitus. Genetically obese (ob/ob) mice, characterized by hyperglycaemia, hyperinsulinaemia, fatty liver and obesity were selected. The impairment of diabetic state with age was associated with increased activities of NADPH producing enzymes, whereas mixed function oxidase system remained unaltered. Phenobarbital reduced serum immunoreactive insulin and plasma glucose levels and decreased gluconeogenesis. Hepatic glucose phosphorylating enzyme activity increased and glucose releasing enzyme activity decreased. The demand for NADPH in drug oxidation reactions, caused by the induction phenomenon, was reflected in the elevated activities of the NADPH producing enzymes in pentose phosphate pathway and in the activities of isocitrate dehydrogenase and malic enzyme from mitochondrial oxidation reactions. Glucose metabolism of lean littermates indicated that phenobarbital induction normalizes impaired intracellular glucose handling but leaves normal glucose metabolism unaltered. Hepatic glucose production rate was related to plasma glucose, NADPH producing enzyme activities and cytochrome P450 content in the obese and lean mice.
 ...
PMID:Effects of enzyme induction therapy on glucose and drug metabolism in obese mice model of non-insulin dependent diabetes mellitus. 250 Oct 61

There were significant changes in enzyme activities and concentrations of metabolites in the blood and liver of cows with fatty livers when compared to normal cows. Blood and liver samples were taken from cows at the abattoir immediately after slaughter. The liver was checked for pathological signs and the samples were divided according to the degree of fatty changes. Three groups were studied: controls showing no gross pathological signs, mild fatty infiltration and severe infiltration. In cows with fatty liver, there were significant increases in the serum activities of isocitric dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), glutamic dehydrogenase (GLDH), lactic dehydrogenase (LDH), malic dehydrogenase (MDH), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and acid phosphatase (ACP). In the fatty liver, the activities of the enzymes, ICDH, G6PDH, LDH, MDH, ALP and malic enzyme (ME) were significantly higher, while sorbitol dehydrogenase (SDH) was significantly lower. While serum total lipid decreased, the opposite was seen in the liver with higher lipid content, mainly due to triglycerides and cholesterol esters. The significant increases in the NADPH generating enzymes ME, ICDH, G6PDH and MDH, which are required for fatty acid synthesis, suggest that the lipids accumulated in the liver are not only of extrahepatic origin, mobilized into the liver, but also arise from increased lipid synthesis in the liver which is induced during the laying down of fat in the liver. Measurement of the serum NADPH generating enzymes may serve as a useful biochemical test specific for fatty liver in cows.
 ...
PMID:Biochemical changes associated with the fatty liver syndrome in cows. 339 48

Excessive fat accumulation in the liver is a common metabolic disorder seen in humans and animals. Fatty liver was induced in the rat by feeding the animals with a sucrose rich diet containing 1% orotic acid for 2-3 weeks. In the sera from fatty liver rats there were significant changes in the level of alanine aminotransferase (+ 68.7%), malic dehydrogenase (+ 77.8%), gamma-glutamyl transpeptidase (- 53.4%) and total lipids (+ 26.6%). There were small to no changes in the levels of aspartate aminotransferase, glucose-6-phosphate dehydrogenase, lactic dehydrogenase, aldolase, malic enzyme, 6-phosphogluconic acid dehydrogenase, alkaline phosphatase and albumin. In fatty liver, significant differences were seen in the levels of glucose 6-phosphate dehydrogenase (+ 235%), malic enzyme (+ 170%), gamma-glutamyl transpeptidase (+ 113%), 6-phosphogluconate dehydrogenase (+ 63%), aspartate aminotransferase (+ 35.6%), malic dehydrogenase (+ 38%), lactic dehydrogenase (+ 37%), and alanine aminotransferase (- 23%). Comparison of the non-fatty part with the fatty part of the fatty liver showed larger changes in the non-fatty part of the liver, suggesting that during the fattening process, there is an induction of enzymes in the liver reaching a peak prior to lipid accumulation, declining thereafter during liver fattening. The increase in NADPH-generating lipogenic enzymes suggests that accumulated fat in the liver is at least partially from de-novo increased synthesis in the liver.
 ...
PMID:Biochemical changes in liver and blood during liver fattening in rats. 377 7

Effects of chronic ethanol consumption, withdrawal and fasting on the free cytosolic NADP+/NADPH ratio and NADPH-regenerating enzyme activities of rat liver were studied. Ethanol consumption was shown to decrease the NADP+/NADPH ratio in non-fasted rats, and both ethanol withdrawal and fasting in ethanol-fed animals appeared to increase the ratio to the normal or higher level. Any treatment of rats caused the complex interaction on hepatic NADPH-regenerating enzyme activities, none of the enzyme activity correlating with the free cytosolic NADP+/NADPH ratio. Relationship between free cytosolic NADP+/NADPH ratio and lipogenic capacity of withdrawn rat liver is discussed, and a hypothesis for development of the fatty liver is suggested.
 ...
PMID:A comparison between effects of chronic ethanol consumption, ethanol withdrawal and fasting in ethanol-fed rats on the free cytosolic NADP+/NADPH ratio and NADPH-regenerating enzyme activities in the liver. 404 9

Monkeys (Macaca nemestrina) were divided into four groups, and each group was fed a particular diet. The variables in the diets were as follows: diet A, 0.3 mg cholesterol/kcal nutrient; diet B, 1.0 mg cholesterol/kcal nutrient; diet C, 0.3 mg cholesterol/kcal nutrient, ethanol (36% of calories); diet D, 1.0 mg cholesterol/kcal nutrient, ethanol (36% of calories). Monkeys on the diets containing ethanol developed fatty liver. Mitochondria from ethanol-fed animals demonstrated significant decreases in uncoupler-stimulated, state 3, and state 4 succinate oxidation activity; respiratory control ratio; and ATP content. Liver microsomes isolated from the ethanol-fed groups demonstrated increased ethanol oxidizing activity with either NADPH or H2O2 as cosubstrate. Aniline hydroxylase and aminopyrine-N-demethylase activities were also elevated in ethanol-fed animals. The alterations in these functional properties were related primarily to ethanol in the diets. Cholesterol, while being less of a perturbant than ethanol, did elicit a significant decrease in cytochrome oxidase activity of mitochondria and a small but statistically significant increase in microsomal-associated ethanol oxidation activity. It appeared to potentiate the effect of ethanol in lowering mitochondrial respiratory control and ATP concentrations.
 ...
PMID:Effect of dietary ethanol and cholesterol on metabolic functions of hepatic mitochondria and microsomes from the monkey, Macaca nemestrina. 702 93

It is well established that chronic ethanol ingestion enhances lipid peroxidation in the liver in vivo and in vitro. The relationship of lipid peroxidation and protein adduct formation to morphologically assessed liver damage remains problematic. To help determine if a relationship exists between lipid peroxidation and liver pathology rats were fed ethanol and a high fat diet by continuous intragastric tube feeding for 72 days, maintaining the blood alcohol levels above 200 mg/dl. This model induced a fatty liver with focal necrosis and fibrosis. This pathology was associated with an increased total cytochrome P450, an increased cytochrome P450 2E1 isoenzyme (CYP2E1), a decrease in the NADPH-cytochrome P450 reductase activity, an increased rate of NADPH oxidation and an increased NADPH-dependent lipid peroxidation in liver microsomes compared to controls. Serum protein adducts with malondialdehyde 4-hydroxynonenal were significantly increased. Thus, the alcohol-induced liver pathology was associated with the induction of CYP2EI, lipid peroxidation, and protein adduct formation. When isoniazid (INH) in therapeutic doses was fed to rats with ethanol these parameters were changed in that central-central bridging fibrosis was increased, as was lipid peroxidation, whereas INH reduced the ethanol-induced decrease in the reductase, the increase in total P450 and CYP2EI, as well as the NADPH oxidation rate and the elevation of serum transaminase levels. The results tend to link central-central bridging fibrosis with increased lipid peroxidation and aldehyde-protein adduct formation caused by ethanol.
 ...
PMID:Effect of ethanol on cytochrome P450 2E1 (CYP2E1), lipid peroxidation, and serum protein adduct formation in relation to liver pathology pathogenesis. 845 37

The effect of emeriamine, a potent inhibitor of the entry of fatty acids into mitochondria on lipid metabolism, was examined. Emeriamine (10 mg/kg body weight) was orally administered to rats under the two different physiological conditions of a 2-day fast or refeeding with a high-carbohydrate diet after a 2-day fast. When rats were refed with a high-carbohydrate diet, serum and hepatic ketone bodies and the levels of free fatty acids decreased, and triglycerides significantly increased compared with fasting rats. However, no significant effect of emeriamine on serum and hepatic lipids was observed between two refeeding groups with or without emeriamine. Conversely, when emeriamine was administered to fasting rats, the levels of serum and hepatic triglycerides increased about 11- and 5-fold, respectively. However, the increased level of hepatic triglycerides was not accompanied by the activities of fatty acid synthetase and NADPH-generating enzymes. The analysis of serum lipoprotein revealed that very low-density lipoprotein consisted of triglyceride-rich particles and there were less apolipoproteins in the fasting rat given emeriamine. We also determined the 120-kDA protein content, which was probably dependent on lipogenesis. The level of 120-kDa protein was greatly increased with or without the administration of emeriamine after refeeding with a high-carbohydrate diet, but the concentration of 120-kDa protein was slight in the fasting rat with emeriamine. These results suggest that specific inhibition of fatty acid oxidation by emeriamine diverted the exogenous fatty acid to the esterification pathway, and induced fatty liver and hypertriglyceridemia under fasting conditions.
 ...
PMID:Hypertriglyceridemia and fatty liver of fasting rats after administration of emeriamine. 878 Sep 69

We recently reported that fatty liver and hypertriglyceridemia are easily induced by the administration of an inhibitor of fatty acid oxidation (emeriamine; (R)-3-amino-4-trimethylaminobutyric acid) to fasting rats, and that these conditions are not accompanied by the increased de novo synthesis of fatty acid [J. Nutr. Sci. Vitaminol., 42, 111-120, (1996)]. To study whether emeriamine-induced fatty liver is affected by nutrients during recovery from fatty acid oxidation inhibition, we fed rats with either a high-carbohydrate (HCHO) diet or a high-fat (HFAT) diet. Rats fed an HCHO diet following the administration of emeriamine showed a marked decrease in serum and hepatic triglycerides, and a marked increase in hepatic glycogen. The lower levels of serum and hepatic triglycerides were accompanied by decreased activities of the NADPH-generating enzymes such as malic enzyme and glucose-6-phosphate dehydrogenase. By contrast, rats fed an HFAT diet showed less significant changes in hepatic triglyceride and glycogen levels. These results suggest a reciprocal relationship between the triglyceride level and glycogen accumulation caused by HCHO diet during recovery from emeriamine.
 ...
PMID:Effects of refeeding diets on emeriamine-induced fatty liver in fasting rats. 898 Dec 52

Effects of dietary carbohydrates on triglyceride production and hepatic lipogenic enzyme activities were examined in Wistar fatty rats, an animal model of noninsulin dependent diabetes mellitus, fed fructose or glucose and were compared with those of Wistar lean rats. Carbohydrates were supplied in 10% drinking solutions for 21 days. As compared with lean rats, Wistar fatty rats were characterized by hyperglycemia, hyperinsulinemia and hypertriglyceridemia, the last of which was associated with an increased hepatic activity of fatty acid synthetase and an increased rate of triglyceride secretion from the liver to the circulation. Feeding fructose to genetically obese diabetic rats produced a threefold increase in the hepatic activity of fatty acid synthetase, a twofold increase in NADPH-generating enzymes (malic enzyme and glucose-6-phosphate dehydrogenase) and a 56% increase in the rate of triglyceride secretion, with a resultant 86% increase in plasma triglyceride concentrations. Feeding glucose produced a similar increase in the activity of NADPH-generating enzymes and triglyceride production in the fatty liver but it differed in producing no change in plasma triglyceride concentrations or hepatic fatty acid synthetase activity. Neither dietary fructose nor glucose changed glycemia or insulinemia. These results show that in genetically obese, diabetic rats feeding fructose and glucose is associated with an increase in hepatic lipogenic enzyme activities and triglyceride production, and suggest that fructose stimulates triglyceride production but impairs triglyceride removal, whereas glucose stimulates both of them.
 ...
PMID:Effects of dietary fructose or glucose on triglyceride production and lipogenic enzyme activities in the liver of Wistar fatty rats, an animal model of NIDDM. 922 59


1 2 3 Next >>