Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The accumulation of triglycerides in the liver has been associated with reduced hepatic function; however, direct evidence that fat accumulation causes decreased liver function is lacking. Hepatocyte monolayers isolated from ruminating calves with an initial low triglyceride concentration were either loaded or not loaded with triglycerides by incubation with 1.5 or 0 mM exogenous nonesterified fatty acids from 12 to 48 h after plating. Basal rates of synthesis of albumin and protein were not affected by triglycerides in the cell. Inclusion of insulin and glucagon from 12 to 72 h after plating increased rates of albumin and protein synthesis. Hepatocytes loaded with triglycerides were less sensitive to the hormonal stimulation of albumin and protein synthesis than were normal hepatocytes. Insulin clearance rates were also lower in hepatocytes loaded with triglycerides than in normal hepatocytes. Decreased insulin clearance and hormonal control of protein synthesis could contribute to the etiology of metabolic disorders that are associated with periparturient fatty liver in dairy cows.
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PMID:Relationship of triglyceride accumulation to insulin clearance and hormonal responsiveness in bovine hepatocytes. 956 77

Liver fatty acid-binding protein (LFABP) is an abundant protein in hepatocytes that binds most of the long chain fatty acids present in the cytosol. It is suggested to be of importance for fatty acid uptake and utilization in the hepatocyte. In the present study, the effects of bovine GH (bGH) and other hormones on the expression of LFABP and its messenger RNA (mRNA) were studied in hypophysectomized rats and in vitro using primary cultures of rat hepatocytes. One injection of bGH increased LFABP mRNA levels about 5-fold after 6 h, but there was no effect of this treatment on LFABP levels. However, 7 days of bGH treatment increased both LFABP mRNA and LFABP protein levels 2- to 5-fold. Female rats had higher levels of LFABP than male rats. Hypophysectomy of female rats, but not that of male rats, decreased LFABP levels markedly. Treatment of hypophysectomized rats with bGH for 7 days as two daily injections or as a continuous infusion increased LFABP levels to a similar degree. This finding indicates that the sex difference in the expression of LFABP is not regulated by the sexually dimorphic secretory pattern of GH. Neither insulin nor insulin-like growth factor I treatment of hypophysectomized rats for 6-7 days had any effect on LFABP mRNA or LFABP levels. In vitro, bGH dose-dependently increased the expression of LFABP mRNA, but only in the presence of insulin. Insulin alone had a marked dose-dependent effect on LFABP mRNA levels and was of importance for maintaining the expression of LFABP mRNA during the culture. Incubation with bGH increased LFABP mRNA levels within 3 h. GH had no effect on LFABP mRNA levels in the presence of actinomycin D, indicating a transcriptional effect of GH. Incubation with glucagon in vitro decreased LFABP mRNA levels markedly, indicating that glucagon, in contrast to GH, has an effect opposite that of insulin on LFABP mRNA expression. It is concluded that GH is an important regulator of LFABP in vivo and in vitro. In contrast to the effect of GH on insulin-like growth factor I mRNA, the presence of insulin was a prerequisite for the effect of GH on LFABP mRNA expression in vitro. The results emphasize the role of GH in the regulation of hepatic fatty acid metabolism.
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PMID:Hormonal regulation of liver fatty acid-binding protein in vivo and in vitro: effects of growth hormone and insulin. 960 75

The present study was designed to define whether maximal removal rate of indocyanine green (ICG Rmax), plasma cyclic 3',5'-adenosine monophosphate (cAMP) response to exogenous glucagon (peak to basal ratio of cAMP level: P/B cAMP) and plasma half-life of galactose (t1/2 galactose) can measure the hepatic functional reserve of fatty liver prepared in rats fed choline-deficient (9 weeks), 2% cholesterol (2 weeks) or 0.25% DL-ethionine (2 weeks) diet. Although changes in cholesterol and phospholipid values in serum during feeding periods differed among the models, histopathologic examinations in the liver of almost all animals revealed intermediate to severe fatty liver with or without fibrosis at each termination. ICG Rmax and P/B cAMP were significantly decreased in rats fed choline-deficient or DL-ethionine diet, implying reductions in hepatic functional mass and disturbances in hepatic cAMP production. Meanwhile, t1/2 galactose showed no change in any of the models, suggesting that glucose metabolisms in the models used may be preserved. These findings demonstrate that ICG Rmax and P/B cAMP can apply to measurement of hepatic surviving reserve of fatty liver with fibrosis.
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PMID:Application of hepatic tolerance tests to the functional reserve assessment in rat models of fatty liver. 963 1

Twenty multiparous cows were fed additional concentrate during the final 30 d prepartum to cause susceptibility to fatty liver. From 14 to 42 d postpartum, all cows were subjected to a protocol to induce fatty liver and ketosis. To test glucagon as a treatment for fatty liver, either glucagon at 10 mg/d or excipient was infused via the jugular vein from 21 to 35 d postpartum. All cows had fatty liver at 14 d postpartum and became ketonemic and hypoglycemic during the induction of ketosis. Glucagon increased plasma glucose to 142% of that of controls throughout the 14-d treatment. The hypoinsulinemia present in cows with fatty liver was not affected by glucagon. Plasma beta-hydroxybutyrate and nonesterified fatty acids were decreased by glucagon. At 6 d postpartum, liver triacylglycerol averaged 12.9% of liver (wet weight basis). Glucagon had decreased triacylglycerol content of livers by 71% at d 35. Glycogen was 1.0% of the wet weight of livers at 6 d in milk, but it was decreased by glucagon to 0.5% at 2 d after glucagon began. Glycogen then increased in cows treated with glucagon until at 38 d in milk liver glycogen was 3.7% versus 1.6% in controls. Our results document that glucagon decreases the degree of fatty liver in early lactation dairy cows, which also decreases the incidence of ketosis after alleviation of fatty liver.
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PMID:Alleviation of fatty liver in dairy cows with 14-day intravenous infusions of glucagon. 1038

The effects of glucagon infusions on expression of mRNA for enzymes that regulate gluconeogenesis were studied in lactating cows. Normal cows and cows with fatty liver that were susceptible to ketosis were assigned to either glucagon-treated or control groups. Glucagon at 0 or 10 mg/d was infused for 14 d beginning at d 21 postpartum. In normal cows, glucagon infusions increased concentrations of both plasma glucagon and glucose, which caused plasma insulin to increase. Consequently, hepatic phosphoenolpyruvate carboxykinase mRNA decreased during wk 1 of glucagon infusions. Glucagon infusions into cows with fatty liver also increased plasma glucagon and glucose, but concentrations of plasma insulin and hepatic phosphoenolpyruvate carboxykinase mRNA did not change. More phosphoenolpyruvate carboxykinase mRNA was present in the livers of cows with fatty liver than in livers of normal cows. In a follow-up experiment with midlactation cows, 3.5-h infusions of glucagon at 14 mg/d increased plasma glucose and insulin and decreased plasma nonesterified fatty acids and hepatic glycogen. Hepatic phosphoenolpyruvate carboxykinase mRNA was decreased 41%, pyruvate carboxylase mRNA was increased 50%, but fructose-1,6-bisphosphatase mRNA did not change. We conclude that the expression of the hepatic phosphoenolpyruvate carboxykinase gene in normal cows is inhibited by insulin to balance elevated carbohydrate status during glucagon infusions; however, inhibited expression of hepatic phosphoenolpyruvate carboxykinase mRNA probably is not involved in the pathogenesis of lactation ketosis.
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PMID:Regulation of messenger ribonucleic acid expression for gluconeogenic enzymes during glucagon infusions into lactating cows. 1038 1

Fasting induces pancreatic secretory lipase, possibly through an increased utilization of fatty acids and/or ketone bodies by the acinar cells. To test this hypothesis, the effects of L-aminocarnitine (ACA), an inhibitor of mitochondrial beta-oxidation and ketone body formation, on the pancreatic enzyme composition were studied in rats. The characteristics and reversibility of the hepatic steatosis produced by ACA in fasted animals were also investigated. In fasted rats, ACA decreased the plasma levels of beta-hydroxybutyrate, glucose and insulin, but increased that of glucagon. Fasting for 3 days increased the pancreatic lipase content by 80%. Administration of ACA (3, 10 or 30 mg kg(-1) daily) for 3 days to fasted rats led to dose-related decreases in pancreatic lipase content, the fasting-induced increase was prevented even by the lowest dose. Nevertheless, ACA in the fasted rats likewise decreased the pancreatic contents of protein, amylase and trypsinogen to varying degrees, suggesting a general defect of protein synthesis. The 3-day treatment with ACA during fasting led to dose-related, marked increases in hepatic weight and triglyceride content. Light and electron microscopy revealed lipid vesicles of varying sizes in the hepatocytes; the fat deposition was predominant in the periportal zones of the hepatic lobules. By means of electron microscopy, lipid vacuoles were observed in the centroacinar cells, but not in the acinar cells of the pancreas. In rats treated with 30 mg kg(-1) of ACA daily for 3 days while they were fasted, cessation of ACA treatment and refeeding with normal chow led to normalization of the pancreatic enzyme contents within 6 days, and gradual and complete disappearance of the hepatic steatosis within 24 days. Microscopy also demonstrated complete recovery in both the liver and the pancreas. The results indicate that pancreatic secretory lipase induction during the adaptive phase of starvation is dependent on an unhindered mitochondrial beta-oxidation of fatty acids and ketogenesis. The dose-related degree of hepatic triglyceride accumulation which can be produced readily by administration of ACA during short-term starvation in the rat may serve as a new, convenient experimental model for studies of fatty liver.
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PMID:Effect of L-aminocarnitine, an inhibitor of mitochondrial fatty acid oxidation, on the exocrine pancreas and liver in fasted rats. 1060 Feb 64

Hepatic lipidosis in cats is a commonly diagnosed hepatobiliary disease of unknown cause. The purpose of this prospective study was to characterize the blood hormone and lipid status of cats with hepatic lipidosis, and to compare this status to that of cats with other types of liver disease and to control cats. Twenty-three cats with hepatic disease were assigned to 1 of 2 groups on the basis of cytopathologic or histopathologic examination of the liver: group 1, hepatic lipidosis (n = 18); or group 2, cholangiohepatitis (n = 5). Ten healthy young adult cats were used as controls. Food was withheld from control animals for 24 hours before blood collection. Concentrations of plasma glucagon and serum insulin, cortisol, thyroxine, triglycerides, cholesterol, phospholipids, and nonesterified fatty acids (NEFAs) were determined in all cats, in addition to routine hematologic and serum biochemical testing. Cats with hepatic lipidosis had higher serum NEFA concentrations than cats with cholangiohepatitis or control cats (P < .05). Cats with cholangiohepatitis had higher serum cholesterol and phospholipid concentrations than those of cats with lipidosis or control cats (P < .05); their plasma glucagon concentrations were higher than those of control cats (P < .05), but were not different from those of cats with hepatic lipidosis. Serum insulin concentrations were significantly higher in control cats than in diseased cats (P < .05), but neither serum insulin nor the insulin to glucagon ratio was significantly different among the cats with hepatic disease. The high concentration of NEFAs in cats with hepatic lipidosis suggests that at least 1 factor in the pathogenesis of this syndrome may involve the regulation of hormone-sensitive lipase.
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PMID:Metabolic and hormonal alterations in cats with hepatic lipidosis. 1066 12

During embryonic development, insulin-like growth factor-II (IGF-II) participates in the regulation of islet growth and differentiation. We generated transgenic mice (C57BL6/SJL) expressing IGF-II in beta cells under control of the rat Insulin I promoter in order to study the role of islet hyperplasia and hyperinsulinemia in the development of type 2 diabetes. In contrast to islets from control mice, islets from transgenic mice displayed high levels of IGF-II mRNA and protein. Pancreases from transgenic mice showed an increase in beta-cell mass (about 3-fold) and in insulin mRNA levels. However, the organization of cells within transgenic islets was disrupted, with glucagon-producing cells randomly distributed throughout the core. We also observed enhanced glucose-stimulated insulin secretion and glucose utilization in islets from transgenic mice. These mice displayed hyperinsulinemia, mild hyperglycemia, and altered glucose and insulin tolerance tests, and about 30% of these animals developed overt diabetes when fed a high-fat diet. Furthermore, transgenic mice obtained from the N1 backcross to C57KsJ mice showed high islet hyperplasia and insulin resistance, but they also developed fatty liver and obesity. These results indicate that local overexpression of IGF-II in islets might lead to type 2 diabetes and that islet hyperplasia and hypersecretion of insulin might occur early in the pathogenesis of this disease.
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PMID:Transgenic mice overexpressing insulin-like growth factor-II in beta cells develop type 2 diabetes. 1072 41

An experiment demonstrating the usefulness of glucagon as a treatment for fatty liver and ketosis in early-lactation dairy cows has been described. This is the first report of the ability of glucagon, or any agent, to promote clearance of lipid from livers of animals suffering hepatic lipidosis. The development and use of glucagon as a therapeutic agent for the fatty-liver complex in dairy cows may provide a powerful management tool to enhance the profitability of the high-producing dairy cow.
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PMID:Glucagon as a potential therapy for ketosis and fatty liver. 1102 40

Leptin has recently been suggested to play a role in the pathogenesis of hepatic steatosis. Consequently, this study was designed to examine the direct effects of portal leptin on the intrahepatic lipid contents in the postabsorptive state. Rat livers (n = 6 per group) were perfused in a recirculating system and portally infused with leptin (0.5 nmol/L, 5 nmol/L, and 25 nmol/L), insulin (10 nmol/L), leptin (5 nmol/L) plus insulin (10 nmol/L), glucagon (1 nmol/L), or vehicle (control). Intrahepatic contents of triglycerides, free cholesterol, cholesteryl esters, and free fatty acids were determined from the lipid extract of frozen livers by capillary gas chromatography. Short-term leptin infusion increased total triglycerides in a concentration-dependent (0.5 nmol/L: 2.8 +/- 0.4 mg/g, 5 nmol/L: 7.0 +/- 0.5 mg/g, 25 nmol/L: 8.3 +/- 1.0 mg/g) and time-dependent manner. Total triglycerides also rose during exposure to insulin plus leptin (7.2 +/- 0.6 mg/g) but fell during glucagon infusion (2.6 +/- 0.2 mg/g; control: 4.3 +/- 0.3 mg/g; P <.05). Leptin, insulin, and glucagon increased intrahepatic free cholesterol (P <.05). Free fatty acids were also higher during leptin exposure (0.5 nmol/L: 1.28 +/- 0.08 mg/g, 5 nmol/L: 0.47 +/- 0.01 mg/g, 25 nmol/L: 0.48 +/- 0.04 mg/g, control: 0.38 +/- 0.03 mg/g; P <.05). In conclusion, hyperleptinemia increases hepatic triglyceride content and may therefore contribute to hepatic steatosis in hyperleptinemic obese patients.
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PMID:Effects of short-term leptin exposure on triglyceride deposition in rat liver. 1105 55


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