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 effect of glutamine on hepatic steatosis and serum amino acid pattern was studied in rats receiving total parenteral nutrition (TPN) with different levels of caloric intake. Rats were divided into four groups; a control group (n = 10) was fed a chow diet and infused with saline only. Three experimental groups (n = 8 to 10) received TPN solutions at energy levels of 25 kcal, 30 kcal, and 35 kcal/100 g body weight, respectively. The experimental groups were maintained with TPN for a period of 6 days. Each experimental group was divided into two subgroups, one of which was supplemented with glutamine, replacing 40% of the total amino acid nitrogen. All of the basal TPN solutions were isonitrogenous and identical in nutrient composition, except for the difference in energy level, which was adjusted with glucose. The results demonstrated that liver fat increased in accordance with the increase of glucose supply, and this increase was mainly due to triglyceride accumulation. Very-low-density lipoprotein-triglyceride and serum free fatty acid were significantly higher in the 30-kcal groups. There were no differences in hepatic lipid content, very-low-density lipoprotein-triglyceride secretion, or hepatic uptake of fatty acids between subgroups with and without glutamine supplementation. It was concluded that glutamine enrichment of a TPN solution did not have any effect on hepatic steatosis in normal rats.
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PMID:Effect of L-glutamine on hepatic lipids at different energy levels in rats receiving total parenteral nutrition. 816 2

Glutamine (Gln) supplementation in total parenteral nutrition (TPN) has been shown to have a preventive effect on high glucose induced hepatic steatosis. This animal study was undertaken to evaluate whether Gln could prevent hepatic steatosis induced by high fat or high glucose infusion. After placement of internal jugular catheters, rats were divided into three groups: control (n = 8), high fat (n = 13) and high glucose (n = 14) groups. The control group was fed with a chow diet and infused with saline alone. The experimental groups were infused with either a high fat (65% of nonprotein calories) or high glucose (83% of total kilocalories) solution. Energy intake was 35 kcal/100 g body weight per day. TPN solutions were isocaloric, isonitrogenous and isovolemic. Each experimental group was divided into two subgroups, with one receiving a Gln supplement to replace 40% of total amino acid nitrogen. The results demonstrated obvious fatty infiltration in the experimental groups, mainly from triglyceride (TG) accumulation. Plasma very low density lipoprotein-triglyceride (VLDL-TG) was significantly lower in the experimental groups than in the control group, suggesting that liver secretion of TG may have been inhibited in the experimental groups. Liver fatty acid synthetase (FAS) activity and plasma free fatty acid were lower in the high fat group than in the control and high glucose groups. There was no difference in hepatic lipids content, FAS activity, VLDL-TG, hepatic uptake of fatty acids and liver histologic change in the subgroups with and without Gln supplementation. Thus, Gln supplementation in a TPN solution has no effect in preventing hepatic steatosis induced by either high glucose or high fat infusion in rats under these experimental conditions.
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PMID:Effects of L-glutamine on induced hepatosteatosis in rats receiving total parenteral nutrition. 852 58

We have analyzed diagnostic efficiencies of the individual "Essential laboratory test" items when these tests were applied to 520 new outpatients in the division of comprehensive medicine in a teaching hospital. The integration of these test results with history-taking and physical examination resulted in 544 primary clinical diagnoses which corresponded to the patient's illness complained and in 361 additional diagnoses unrelated to their chief complaints but found by chance by the addition of the test results. Clinical usefulness of these test items were variable depending on the disease category, demonstrating a superior diagnostic efficiency in infectious or inflammatory diseases, liver and biliary tract diseases, hematological disorders or metabolic diseases such as hyperlipidemia and diabetes mellitus, but a lesser degree of usefulness in gastro-intestinal or neurogenic diseases. Urine urobilinogen could not establish its clinical usefulness because of extremely low diagnostic sensitivity even in liver diseases. The leukocyte differential count provided confirmatory information for infectious or inflammatory diseases and was helpful for the estimation of the etiologic nature of infectious diseases. This study failed to terminate a controversy for the adoption of sialic acid instead of erythrocyte sedimentation rate (ESR) in the "Essential laboratory test" items, since the former test showed lower sensitivity, even though higher specificity, in infectious or inflammatory status than ESR. Low albumin globulin ratio (A/G) revealed equivalent diagnostic sensitivity and specificity to the elevated levels in alpha 1 and/or alpha 2 globulin fractions in infectious or inflammatory status, being helpful for the evaluation of patient's general condition at a glance. Incidental analysis for diagnostic values of cholinesterase and random blood glucose for the detection of fatty liver and diabetes mellitus, respectively, suggested that these two tests may be included in the "Essential laboratory tests". Simultaneous measurement of serum creatinine and blood urea nitrogen levels was recommended for the ambulatory screening of renal insufficiency, rather than the measurement either alone. The results in this study provide scientific bases on the usefulness of the individual test items and should be taken into account in the next version of the "Essential laboratory tests".
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PMID:The results of the "essential laboratory tests" applied to new outpatients--re-evaluation of diagnostic efficiencies of the test items. 875 34

Systemic carnitine-deficient juvenile visceral steatosis (JVS) mice exhibit decreased expression of some liver-selective genes including those for the urea cycle enzymes during the infantile period. At 25 days, carbamoylphosphate synthetase (CPS) mRNA level was remarkably low in the liver of JVS mice, and the HNF-4 and C/EBP-alpha mRNA contents were also reduced. HNF-3 alpha and C/EBP-beta mRNAs were slightly higher in the liver of JVS mice, and HNF-1 mRNA remained normal. These results, together with the developmental changes of these transcription factor mRNA levels, suggest that HNF-4 and C/EBP-alpha are involved in the suppression of CPS expression. If JVS mice survived the crisis at 4-5 weeks, their body weight caught up with that of control mice around 7 weeks. The steady-state levels of CPS and argininosuccinate synthetase (ASS) mRNAs in the liver of JVS mice were normalized by no later than 8 weeks. Starvation for 48 h caused an increase of about twofold in CPS and ASS mRNA levels in the liver of control mice, while the same treatment failed to increase their levels in the liver of JVS mice. The starvation similarly caused increases in HNF-4 and C/EBP-beta mRNA levels in the liver of both control and JVS mice, but the increases were significantly less in JVS mice than in control mice. Thus, the lack of induction of CPS and ASS mRNAs during development and under starvation in JVS mice correlated with the lower induction of HNF-4 and C/EBP-alpha mRNAs, and of HNF-4 and C/ EBP-beta mRNAs, respectively. Furthermore, all these changes seemed to correlate with the presence of fatty liver and the high serum free fatty acid levels, suggesting that disturbance of fatty acid metabolism affects nitrogen metabolism at least in part via altered gene expression of transcription factors such as HNF-4, C/EBP-alpha, and C/EBP-beta.
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PMID:Suppressed expression of the urea cycle enzyme genes in the liver of carnitine-deficient juvenile visceral steatosis (JVS) mice in infancy and during starvation in adulthood. 905 9

Alcohol-related liver disease is a major cause of morbidity and mortality in the United States. Alcoholic liver disease encompasses a clinicohistological spectrum, including fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Fatty liver is a benign and reversible condition, but progression to alcoholic hepatitis and cirrhosis is life-threatening. Alcoholic hepatitis is diagnosed predominantly on clinical history, physical examination, and laboratory testing, although liver biopsy is often necessary to secure the diagnosis. The major focus of management is abstinence from alcohol, supportive care, treatment of complications of infection and portal hypertension, and maintenance of positive nitrogen balance through nutritional support. Corticosteroid therapy is controversial but should be considered in patients with a discriminant function greater than 32 and/or presence of spontaneous hepatic encephalopathy in the absence of infection, gastrointestinal bleeding, and renal failure. The only curative therapy for advanced alcoholic cirrhosis is liver transplantation. Several recent advances in understanding the pathogenesis of alcoholic liver disease may lead to novel future treatment approaches, including inhibition of tumor necrosis factor a, antioxidant therapy, stimulation of liver regeneration, and stimulation of collagen degradation.
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PMID:Pathogenesis, diagnosis, and treatment of alcoholic liver disease. 1160 86

Type B lactic acidosis is a rare and often fatal complication seen in patients receiving the nucleotide analogues zidovudine, stavudine, didanosine, and lamivudine. We describe a case of a 51-year-old human immunodeficiency virus (HIV)-positive woman receiving three nucleotide analogues. She presented with nausea, vomiting, abdominal pain, and hepatic steatosis. Signs of mitochondrial toxicity were demonstrated by diffuse myopathy and pancreatitis. Serum riboflavin levels documented a deficiency that was treated with 50 mg of riboflavin daily. Immediately after treatment, serum blood urea nitrogen level, lactic acid levels, and arterial blood pH all returned to normal values. Her signs of mitochondrial toxicity also improved after treatment with riboflavin. Successful reversal of the patient's type B lactic acidosis after riboflavin therapy suggested that riboflavin deficiency plays a direct role in the development of nucleotide analogue-induced lactic acidosis. It is impossible to predict which patients are predisposed to the development of this syndrome. For this reason, it may be important to screen and treat riboflavin deficiency in patients on nucleoside analogues.
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PMID:Emerging role of riboflavin in the treatment of nucleoside analogue-induced type B lactic acidosis. 1178 75

Our understanding of the mechanisms involved in the development of alcohol-induced liver disease has increased substantially in recent years. Specifically, reactive oxygen and nitrogen species have been identified as key components in initiating and possibly sustaining the pathogenic pathways responsible for the progression from alcohol-induced fatty liver to alcoholic hepatitis and cirrhosis. Ethanol has been demonstrated to increase the production of reactive oxygen and nitrogen species and decrease several antioxidant mechanisms in liver. However, the relative contribution of the proposed sites of ethanol-induced reactive species production within the liver is still not clear. It has been proposed that chronic ethanol-elicited alterations in mitochondria structure and function might result in increased production of reactive species at the level of the mitochondrion in liver from ethanol consumers. This in turn might result in oxidative modification and inactivation of mitochondrial macromolecules, thereby contributing further to mitochondrial dysfunction and a loss in hepatic energy conservation. Moreover, ethanol-related increases in reactive species may shift the balance between pro- and anti-apoptotic factors such that there is activation of the mitochondrial permeability transition, which would lead to increased cell death in the liver after chronic alcohol consumption. This article will examine the critical role of these reactive species in ethanol-induced liver injury with specific emphasis on how chronic ethanol-associated alterations to mitochondria influence the production of reactive oxygen and nitrogen species and how their production may disrupt hepatic energy conservation in the chronic alcohol abuser.
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PMID:A review of the role of reactive oxygen and nitrogen species in alcohol-induced mitochondrial dysfunction. 1286 85

Chronic alcohol consumption may lead to primary and secondary malnutrition. In particular, protein energy malnutrition not only aggravates alcoholic liver disease but also correlates with impaired liver function and increased mortality. Therefore, in these patients, adequate nutritional support should be implemented in order to improve their prognosis. Clinical trials addressing this issue have shown that nutritional therapy either enterally or parenterally improves various aspects of malnutrition, and there is increasing evidence that it may also improve survival. Therefore, malnourished alcoholics should be administered a diet rich in carbohydrate- and protein-derived calories preferentially via the oral or enteral route. Micronutrient deficiencies typically encountered in alcoholics, such as for thiamine and folate, require specific supplementation. Patients with hepatic encephalopathy may be treated with branched-chain amino acids in order to achieve a positive nitrogen balance. Fatty liver represents the early stage of alcoholic liver disease, which is usually reversible with abstinence. Metadoxine appears to improve fatty liver but confirmatory studies are necessary. S-adenosyl-L-methionine may be helpful for patients with severe alcoholic liver damage, since various mechanisms of alcohol-related hepatotoxicity are counteracted with this essential methyl group donor, while a recent large trial showed that the use of polyenylphosphatidylcholine is of limited efficacy.
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PMID:Review article: Nutritional therapy in alcoholic liver disease. 1294 Sep 21

The study population in this report by Lin et al. was ob/ob mice that have an inherited genetic deficiency of the appetite-suppressing hormone leptin. These mice develop hyperinsulinemia, insulin resistance, and fatty livers. Compared with their lean littermates and wild-type C57BL-6 mice, ob/ob mice have hepatomegaly. In this study, the authors compared three different groups of adult mice (aged 8-10 wk), including male ob/ob C57BL-6 mice, their lean littermates, and wild-type C57BL-6 mice of the same age and sex. The primary purpose of this study was to test the efficacy of metformin for treatment of fatty liver disease in obese, ob/ob mice that develop hyperinsulinemia or insulin resistance and fatty livers. Metformin therapy was found to eliminate fatty liver disease in this model. The potential mechanisms of the action of metformin were the inhibition of hepatic tumor necrosis factor (TNF)alpha and several TNF-inducible responses, which are likely to promote hepatic steatosis and necrosis. In these experiments, ob/ob mice were divided into three treatment groups. Group 1 consisted of eight mice that were treated with metformin and permitted to consume a nutritiously replete liquid mouse diet ad libitum. Mice in group 2 (n = 8) did not receive metformin but were pair-fed the same volume of liquid diet that the mice in the metformin-treated group had consumed on the previous day. Obese ob/ob mice in group 3 (n = 4) and lean mice received no metformin, as with the mice in group 2, but were permitted to consume the liquid diet ad libitum. Liquid diet was given to facilitate accurate daily comparison of food intake among the various treatment groups. All mice were weighed at the beginning of the study and weekly thereafter until killed and then sera, fat, and liver tissues were collected. Tissues were either fixed in buffered formalin and processed from the deceased mice for histology or snap frozen in liquid nitrogen and stored until RNA and proteins were isolated. The feeding protocol was repeated with a second group of 18 ob/ob mice. After 4 wk, hepatocytes were obtained by in situ liver perfusion with collagenase and assayed for cellular adenosine triphosphate (ATP) content. In each experiment, hepatocytes isolated from 3 mice from each treatment group were suspended in a medium and pooled for subsequent analysis to evaluate cell viability, determine the number of obtained cells, and to assay cellular ATP content. These experiments were repeated using another 3 mice from each treatment group, so that analysis of hepatocytes took place from six ob/ob mice in each feeding group.Hepatic steatosis was decreased significantly only in the metformin-treated group. The authors found that metformin's beneficial effect on the fatty liver disease of mice was not due to its ability to constrain hyperphagia, nor due to decreased caloric ingestion, because the daily caloric intakes of the metformin-treated mice and the pair-fed control mice were virtually identical. These caloric intakes were consistently approximately 20% less than that of another obese control group that was permitted to consume diet ad libitum. The authors also observed no significant effect of metformin on serum glucose concentration from fed, ob/ob mice. Metformin is known to reduce hyperinsulinemia by about 40% in both of these obese hyperinsulinemic and insulin-resistant rodent strains. In conclusion, Lin et al. documented that metformin improves fatty liver disease and reverses hepatomegaly, steatosis, and aminotransferase abnormalities in mice. In addition, the authors suggest that metformin might inhibit dieting-induced redistribution of lipid from the liver to adipose tissue depots. In summary, this study identifies a potential treatment for fatty liver disease in humans.
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PMID:Current biochemical studies of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis suggest a new therapeutic approach. 1449 93

Glycerol can alleviate the symptoms of ketosis when delivered as an oral drench. The addition of glycerol to the diet would eliminate the need for restraining cows for drenching yet deliver a glucogenic substrate, alleviate the fatty liver-ketosis complex, and improve lactational performance. For this study, 21 multiparous and 9 primiparous Holstein cows blocked by parity and expected calving date were used in a randomized block design to evaluate the effects of feeding glycerol from 14 d prepartum to 21 d in milk (DIM). Treatments (kg/d dry matter basis) were 0.86 of cornstarch (control), 0.43 cornstarch + 0.43 glycerol (LG), or 0.86 glycerol (HG), topdressed and hand-mixed into the upper one-third of the daily ration. All cows were fed a common diet from 22 to 70 DIM. Prepartum dry matter intake (DMI) was greater for cows fed the control diet compared with LG or HG (13.3, 10.8, and 11.3 +/- 0.50 kg/d, respectively). Prepartum plasma glucose, insulin, beta-hydroxybutyrate, nonesterified fatty acids, and ruminal profiles were not affected by treatments. Rumen fluid collected postpartum from cows fed LG and HG had greater total volatile fatty acids, greater molar proportions of propionate, and a decreased ratio of acetate to propionate. Furthermore, concentrations of butyrate tended to be greater in rumens of cows fed LG and HG. Postpartum concentrations of glucose in plasma were greatest for cows fed the control diet relative to LG and HG (66.0 vs. 63.1 and 58.4 mg/dL, respectively) and decreased sharply at 21 DIM, after treatments ended, for cows fed HG (diet x day interaction). Body weight and condition loss, plasma nonesterified fatty acids, and liver lipids during the first 21 DIM were similar among treatments. Postpartum DMI was not affected by treatments; however, a tendency was observed for a diet x day interaction for body weight, as cows fed LG gained more body weight from 21 to 70 DIM relative to cows fed HG. Yield of energy-corrected milk during the first 70 DIM tended to be greatest for cows fed the control diet. The LG and HG diets decreased urea nitrogen concentrations in milk relative to controls. Based upon prepartum DMI and concentrations of glucose and beta-hydroxybutyrate in blood postpartum, feeding glycerol to dairy cows at the levels used in this experiment increased indicators used to gauge the degree of ketosis in dairy cattle.
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PMID:Feeding glycerol to transition dairy cows: effects on blood metabolites and lactation performance. 1554 83


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