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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 in rats is associated with an infusion of excessive carbohydrate calories. Previous work from this laboratory suggested that this is associated with an elevated portal insulin/glucagon molar ratio (I/G) and is reversed by parenteral glucagon administration. Although hepatic steatosis is not related to essential fatty acid deficiency, addition of lipid to total parenteral nutrition (TPN) has been reported as being protective against the development of hepatic steatosis. Therefore, we propose that lipid may exert its salutary effect via an alteration of the I/G ratio. To test this hypothesis, adult rats (seven per group) received internal jugular catheters: group 1, saline (3 mL/h) plus chow ad libitum; group 2, 25% dextrose base TPN; group 3, 17% dextrose base TPN + 2.5% lipid; group 4, 25% dextrose base TPN + 2.5% lipid. At 7 days, portal and peripheral venous blood was drawn for insulin and glucagon radioimmunoassay and liver function tests; livers were removed for histology and lipid content determination. Panlobular vacuolization, on histology, and lipid content were excessive in group 2, and the portal I/G was increased because of elevated portal insulin. In contrast, portal venous insulin and I/G did not increase, and hepatic steatosis was absent in groups 3 and 4. The results suggest that the addition of lipid to TPN in rats decreases the portal insulin level and lowers the portal I/G, and thereby prevents hepatic steatosis.
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PMID:Addition of lipid to total parenteral nutrition prevents hepatic steatosis in rats by lowering the portal venous insulin/glucagon ratio. 155 3

The hepatic toxicity of TPN that is seen clinically appears to be multifactorial in origin. Most patients develop a combination of hepatic steatosis with evidence of cholestasis and abnormalities in liver function. The model that we have studied is one of pure hepatic steatosis since, on repeated study, these rats do not develop any liver function abnormalities. It is unclear whether this is related to the fact that these are short-term experiments, that rat livers respond differently from humans, or that rats do not have gallbladders. It has not been possible to carry these experiments out beyond 3 weeks since the rats develop bacterial colonization of the central lines as well as evidence of line sepsis. thus confounding the issue of hepatic toxicity being due to the TPN or to sepsis. One hypothesis is that hepatic steatosis is an early marker of liver toxicity and that prevention or reversal of hepatic steatosis may protect the liver from further abnormality. Insulin and glucagon seem to play a critical role in the development of TPN-associated hepatic steatosis. Specifically, an elevated portal venous insulin-glucagon molar ratio appears to be the primary stimulus and any treatment that lowers this ratio should diminish hepatic steatosis. The use of glucagon as a treatment modality is new. We have found no evident side effects of low dose glucagon in rats when it is added to the TPN solution. Glutamine has received much attention recently as a nutritional pharmacological agent in ameliorating some of the intestinal complications of parenteral nutrition and is well tolerated when administered appropriately. Intravenous lipid administration is an important nonprotein calorie source, especially when a high dextrose base cannot be used, and plays a role as well in preventing the development of hepatic steatosis. Thus, it is suggested that the clinical treatment of hepatic steatosis during TPN can be safely performed using any one, or a combination, of these modalities and without having to discontinue the TPN infusions. Since we observed no deterioration of liver function in rats receiving TPN for up to 2 weeks, we cannot completely relate these findings and recommendations to the hepatic dysfunction seen clinically with the use of TPN. Additional study will be required before this can be conclusively determined.
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PMID:Pathogenesis of hepatic steatosis during total parenteral nutrition. 190 28

Infusion of total parenteral nutrition (TPN) with excess carbohydrate calories leads to hepatic steatosis in rats and is associated with an elevated portal insulin/glucagon molar ratio. Previously we have shown that adding glucagon to TPN prevents and reverses hepatic steatosis in rats, possibly by increasing hepatic lipid export. It has been reported that steatosis is eliminated in rats by the addition of L-glutamine to TPN. In this study, we examined the effect of glutamine on portal insulin and glucagon levels and the development of hepatic steatosis. Adult rats (n = 19) received internal jugular catheters: Group 1 (n = 6), saline (3 cc/hr) and chow ad libitum; Group 2 (n = 7), 25% dextrose base TPN; Group 3 (n = 6), 25% dextrose base TPN with 2% glutamine. The infusion rate of TPN was 1.2 cc/100 g body wt/hr. Daily nitrogen balance was determined and at 7 days, portal venous blood was drawn for insulin and glucagon radioimmunoassay, livers were removed for histology and lipid content determination, and the small intestines were removed for mucosal protein and DNA content determination. Panlobular vacuolization of the hepatocytes was noted on histology in Group 2 (TPN) while Group 1 (chow) and Group 3 (TPN + glutamine) showed normal liver morphology. Hepatic lipid content was significantly elevated in Group 2 (P less than 0.05). The portal insulin/glucagon molar ratio was increased because of excessive portal venous insulin in Group 2 (TPN). In contrast, portal glucagon was significantly elevated while the insulin/glucagon ratio and hepatic lipid content did not increase above control levels in the glutamine-supplemented Group 3 rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Addition of L-glutamine to total parenteral nutrition and its effects on portal insulin and glucagon and the development of hepatic steatosis in rats. 211 67

Since the original description 26 years ago, of the hepatic glycogen synthetase deficiency, only one more case was reported in 1977. We present the studies carried out on an Argentine boy of Italian ancestry who at age 21 months, showed signs of hepatic deficiency with mild clinical symptoms which contrasted with a remarkable fatty liver degeneration. A totally atypic reaction to fructose overload (Table 1, Fig. 1) was the first key to the diagnosis. Glucose levels were not significantly modified by glucagon after 12-hours fasting, but it did increase the glycemia, with decrease of lactate and alanine 3 hours after-meal (Fig. 2a, b). The 24-hours metabolic profile showed fasting hypoglycemia, hyperketonemia, low alanine concentrations and mild lactatemia and hyperglycemia and a net post-prandial increase of lactate (Fig. 3). This profile when reduced to 14 hours, 12-fasting hours and 2-postprandial hours (Fig. 4), revealed similar alterations in an asymptomatic younger brother. The development of the investigation led to a second hepatic biopsy which confirmed hepatic steatosis and to an ultrastructural study, which showed subcellular alterations in the liver and also in muscle (Fig. 5). Moreover low content of hepatic glycogen was observed along with glycogen synthetase activity between 20-25% that of controls, being normal the enzyme activity in muscle and fibroblasts cultured from a skin biopsy (Table 2). The clinical pattern mainly without hypoglycemia, convulsions and/or mental retardation and a normal height and body mass development, allowed us to postulate that this Argentine report would be a mild variant of the disease formerly described and would be correlated with a partial deficiency of the hepatic glycogen synthetase.
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PMID:[Hepatic glycogen synthetase deficiency or glycogen storage disease-zero. Mild phenotype with partial enzymatic defect]. 213 Feb 23

Alcoholic liver disease presents a wide spectrum of clinical manifestations ranging from mild asymptomatic fatty liver to alcoholic hepatitis and severe life-threatening liver failure with ascites, hemorrhaging esophageal varices, and encephalopathy. Although still poorly understood, the mechanism of this injury is probably the result of numerous direct toxic and metabolic effects of alcohol on the hepatocyte. Therapy consists primarily of abstinence and supportive care. However, several newer treatments are actively being studied. These include prednisolone, anabolic steroids, glucagon and insulin, propylthiouracil, and cyanidanol. Colchicine is promising as an agent to inhibit fibrosis. Complications of cirrhosis, including ascites and variceal hemorrhage, are the result of end stage disease. A return to old techniques of ascitic fluid management suggests that therapeutic large-volume paracentesis with albumin infusion is a safe and effective form of therapy. Variceal hemorrhage is best treated with sclerotherapy, vasoconstrictors, and balloon tamponade. Little has been done to alter the ultimately dismal prognosis and long-term survival of alcoholic liver disease.
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PMID:Alcoholic liver disease. 222 93

In this study, the author intended to examine the validity of the inhaled hydrogen gas clearance method (i-H2) for determination of the hepatic blood flow (HBF), and also to show some applicabilities of the method in experimental animals and patients with liver diseases. Simultaneous determinations of HBF by i-H2 and electromagnetic flowmetry in rabbits revealed an excellent correlation between the values obtained by the two methods. Moreover, HBF in rabbits measured by i-H2 varied in parallel with that by thermocouple flowmetry or laser Doppler velocimetry after administration of norepinephrine, propranolol or glucagon. In carbon tetrachloride-treated rats, HBF measured by i-H2 correlated better with the severity of damage in the sinusoidal structure than the severity of hepatic cell injury or the serum levels of transaminases. HBF as determined by i-H2 was significantly decreased in acute hepatitis (AH), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), liver cirrhosis (LC) and fatty liver. Reduced HBF in AH returned to normal during recovery of the disease. The ratio of HBF in tumor/normal tissue was greater than 1.0 for hepatocellular carcinoma in contrast to the ratio of less than 1.0 for metastatic liver carcinoma. Propranolol caused a decrease in HBF by 31%, and vasopressin by 39% in patients with CIH or LC. In contrast, glucagon induced its increase by 65%, 35% and 17%, respectively, in patients with CIH, AH and LC.
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PMID:[Measurement of hepatic blood flow by the hydrogen gas clearance method. Experimental and clinical observations]. 236 96

Infusion of total parenteral nutrition (TPN) with excess carbohydrate calories leads to hepatic steatosis in rats that is associated with an elevated portal insulin/glucagon molar ratio. Previously we have shown that adding glucagon to TPN prevents hepatic steatosis in rats. In this study we attempted to reverse the steatosis by adding glucagon to TPN after 1 week of TPN alone. Adult rats (n = 28) received internal jugular catheters: Group 1 (n = 7), saline (3 cc/h) and chow ad libitum; Group 2 (n = 7), 25% dextrose base TPN solution for 1 week; Group 3 (n = 7), 25% dextrose base TPN for 2 weeks; Group 4 (n = 7), 25% dextrose base TPN for 1 week and then glucagon (15 micrograms/100 g/day) added to TPN for the second week. The infusion rate of TPN was 1.2 ml/100 g/hr (40% kcal greater than control). At 7 days (Group 2) and 14 days (Groups 1, 3, and 4) portal and peripheral venous blood levels were drawn for insulin and glucagon radioimmunoassay, blood glucose determination, and liver function tests; livers were removed for histology and lipid content determination. Blood glucose was equivalent among all groups. Liver function tests were within normal limits. Panlobular vacuolization of the hepatocytes was noted on histology in Groups 2 and 3. Hepatic lipid content was significantly elevated in Group 3. The portal insulin/glucagon molar ratio was increased because of excessive portal venous insulin in Groups 2 and 3 (P less than 0.05 by ANOVA). In contrast, portal venous insulin and the insulin/glucagon molar ratio did not increase in Group 4 and hepatic lipid infiltration was absent when glucagon was added to the TPN solution after 1 week of TPN solution alone. The results suggest that the addition of glucagon to hypertonic dextrose TPN is not only protective in preventing hepatic steatosis, but may reverse steatosis, possibly by increasing hepatic lipid export.
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PMID:Reversal of hepatic steatosis in rats by addition of glucagon to total parenteral nutrition (TPN). 249 33

Feed restriction and dietary 1,3-butanediol were used with lactating goats in an attempt to induce metabolic changes characteristic of bovine lactation ketosis and fatty liver. In Experiment 1, midlactation goats were fed 80, 102, or 114% of metabolizable energy requirements and 0, 50, or 100 g/d of 1,3-butanediol. Concentration of beta-hydroxybutyrate in blood plasma decreased with increasing metabolizable energy but was increased greatly at 2 h after goats were fed 50 or 100 g butanediol and remained elevated at 6 h postfeeding with 100 g of butanediol. Concentration of glucose in plasma was decreased at 2 and 6 h postfeeding in goats fed 100 g of butanediol. In Experiment 2, goats in early lactation were fed for ad libitum intake or were restricted to 70% of ad libitum intake with 1,3-butanediol included at 10% of diet DM. The treatment decreased milk production, increased concentrations of beta-hydroxybutyrate and nonesterified fatty acids, and decreased the concentration of insulin and the insulin to glucagon ratio in plasma. Concentrations of glucose, acetate, and glucagon in plasma were not affected. After 28 d of treatment, concentration of total lipid in liver was increased, but concentrations of glycogen and triglyceride were unaffected. Changes caused in goats by feed restriction plus dietary 1,3-butanediol were characteristic of subclinical lactation ketosis in cows, but the response was more moderate than seen previously in cows.
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PMID:Metabolic responses of lactating goats to feed restriction and dietary 1,3-butanediol. 262 43

To elucidate if the presence of fatty liver and hypertriglyceridemia (HTG) influences pancreatic A-cell function in obesity, basal and arginine-stimulated glucagon (IRG) secretions were studied in 7 normal subjects and in 28 moderately obese patients (OB) with normal glucose tolerance. The patients were divided into 4 groups, based on the presence of fatty liver and/or HTG. BMI was similar in all four obese groups. Basal IRG, as well as the sum of secretory response to arginine, namely sigma IRG values, were significantly (p less than 0.01) higher in the OB subgroup having both fatty liver and HTG than in the other three groups; these values were similar in subgroups of OB without fatty liver, and showed no significant difference from the normals. Basal and sigma IRG values in all OB correlated well with the degree of fatty liver and HTG, demonstrating that by stepwise analysis the effects of fatty liver and HTG were independent for basal and sigma IRG values. These results suggest that the combination of fatty liver and HTG may serve as a good predictor of hyperglucagonemia in simple obesity, and, hence, metabolic heterogeneity among obese patients should be considered in evaluating A-cell function.
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PMID:Elevated pancreatic glucagon in moderately obese patients: relationship of fatty liver and hypertriglyceridemia. 273 44

Recently numerous reports show deleterious effects of alcohol abuse on pregnant women giving their children a high risk of stillbirth and/or several developmental abnormalities and mental retardation, i.e. the Fetal alcohol syndrome (FAS). In the present study, the effects of maternal alcohol consumption on lipid metabolism in the litter liver were investigated in rats. These rats showed not only quite less lipid deposition in spite of large amount of alcohol consumption up to adulthood, but also showed increased FFA oxidation in the livers. In addition, increased level of very low density lipoprotein and hypoglucagonemia were found. 40 micrograms/kg of glucagon which is known as an inhibitory factor of apoprotein production in the liver, was injected for 2 weeks into the rat tail vein and resulted in apparent fatty liver and hypolipoproteinemia. Norepinephrine injection (1 mg/kg) caused plasma glucagon to be depressed in the rat as compared with adult alcohol rats. Plasma cyclic AMP response to glucagon was also depressed in these rats. From these results, it is suggested that the deranged glucagon secretion from the pancreas and lowered glucagon-induced cyclic AMP response would relate to the abnormal lipoprotein metabolism in the rat.
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PMID:[Experimental studies on lipoprotein metabolism in rats reared with liquid alcohol diet from the fetal life]. 298 81


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