Nonalcoholic fatty liver disease.
Explore the source record for details and available documents.
Adrenal Cortex Hormones↗
SEARCH · Search PubMed
Results for “FATTY LIVER”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Human liver fatty acid binding protein cDNA and amino acid sequence. Functional and evolutionary implications.
Human liver fatty acid binding protein (L-FABP) cDNA clones were identified in a liver cDNA library. The two longest clones were completely sequenced. The nucleotide sequence predicts a protein of 127 amino acid residues. Identity of the clones was confirmed by limited amino acid sequence analysis of purified human L-FABP peptides and Edman degradation of radiolabeled in vitro translated FABP. Statistical analysis of the amino acid and mRNA sequences of human L-FABP, rat L-FABP, rat intestinal (I-) FABP, and mouse 422 protein indicates that the human and rat L-FABPs are highly homologous and that L-FABP and I-FABP diverged a long time ago (approximately 650-690 million years ago), although they are more closely related to each other than either of them is to 422 protein. Secondary structure predictions from the primary sequence of human and rat L-FABP reveal a region (residues 12-30) that might be the putative fatty acid binding domain of the two L-FABPs. Knowledge of the primary amino acid sequence of L-FABP and possible functional domains will be pivotal in further defining and understanding the mechanism of ligand binding and transfer by this protein.
Amino Acid Sequence↗
[Acute fatty liver in pregnancy--treatment of hemorrhagic diathesis].
This case report describes the successful treatment of a patient suffering from acute fatty liver of pregnancy. Results of treatment presented in the literature are discussed, as well as suggestions for treatment of hemorrhagic diathesis.
Adult↗
[Clinical and experimental study on treatment of fatty liver of phlegm-dampness stagnation type by zhiganle capsule].
OBJECTIVE: To explore the mechanism of Zhiganle capsule (ZGLC) in treating fatty liver of Phlegm-Dampness Stagnation type. METHODS: One hundred and forty-six patients were treated with ZGLC, the effects were observed and compared with those treated with Dongbao Gantai (DBGT,) tablets as control. The effect of ZGLC on ethionine induced hyperlipemia model rats was also observed. RESULTS: The effect of ZGLC was obviously better than those of DBGT in relieving or removing symptoms, normalizing the ultrasonic abnormal findings, lowering the serum levels of lipid and enzyme and improving hemorrheologic properties. Experimental study showed that ZGLC could reduce the blood lipids, inhibit the lipid deposition in liver. As compared with the model group, level of triglyceride in the ZGLC treatment group were much lowered (P < 0.01) and the effect was better than those in the control group. CONCLUSIONS: ZGLC has the effect of reducing blood triglyceride level, inhibiting lipid deposition in liver and improving hemorrheologic properties.
Adult↗
Nonalcoholic fatty liver disease: from steatosis to cirrhosis.
Nonalcoholic steatohepatitis (NASH), the lynchpin between steatosis and cirrhosis in the spectrum of nonalcoholic fatty liver disorders (NAFLD), was barely recognized in 1981. NAFLD is now present in 17% to 33% of Americans, has a worldwide distribution, and parallels the frequency of central adiposity, obesity, insulin resistance, metabolic syndrome and type 2 diabetes. NASH could be present in one third of NAFLD cases. Age, activity of steatohepatitis, and established fibrosis predispose to cirrhosis, which has a 7- to 10-year liver-related mortality of 12% to 25%. Many cases of cryptogenic cirrhosis are likely endstage NASH. While endstage NAFLD currently accounts for 4% to 10% of liver transplants, this may soon rise. Pathogenic concepts for NAFLD/NASH must account for the strong links with overnutrition and underactivity, insulin resistance, and genetic factors. Lipotoxicity, oxidative stress, cytokines, and other proinflammatory mediators may each play a role in transition of steatosis to NASH. The present "gold standard" management of NASH is modest weight reduction, particularly correction of central obesity achieved by combining dietary measures with increased physical activity. Whether achieved by "lifestyle adjustment" or anti-obesity surgery, this improves insulin resistance and reverses steatosis, hepatocellular injury, inflammation, and fibrosis. The same potential for "unwinding" fibrotic NASH is indicated by studies of the peroxisome proliferation activator receptor (PPAR)-gamma agonist "glitazones," but these agents may improve liver disease at the expense of worsening obesity. Future challenges are to approach NAFLD as a preventive public health initiative and to motivate affected persons to adopt a healthier lifestyle.
Animals↗
Amino acid sequences of pyridoxal 5'-phosphate binding sites and fluorescence resonance energy transfer in chicken liver fatty acid synthase.
The amino acid sequences associated with pyridoxal 5'-phosphate binding sites in chicken liver fatty acid synthase have been determined: a site whose modification causes selective inhibition of the enoyl reductase activity and a site (site I) that is not associated with enzymatic activity. The amino acid sequences of peptides obtained by trypsin hydrolysis of the pyridoxamine 5'-phosphate labeled enzyme were determined. For the site associated with enoyl reductase activity, the sequence similarities between chicken and goose are extensive and include the sequence Ser-X-X-Lys, a characteristic structural feature of pyridoxamine enzymes. In addition, the spatial relationships between the pyridoxal 5'-phosphate binding sites and reductase site(s) have been studied with fluorescence resonance energy-transfer techniques. The distances between site I and the enoyl reductase and beta-ketoacyl reductase sites are greater than 50 and 41-44 A, respectively. The distance between the two reductase sites is greater than 49 A.
Amino Acid Sequence↗
Inhibition of pigeon liver fatty acid synthetase by specific modification of lysine residues with 2,4,6-trinitrobenzenesulphonic acid.
Pigeon liver fatty acid synthetase was inactivated irreversibly by 2,4,6-trinitrobenzenesulphonic acid (TNBS). Biphasic inactivation of the enzyme was observed with the inhibitor. NADPH provided protection to the enzyme against inactivation by TNBS and the extent of protection increased with NADPH concentration indicating that the essential lysine residues are present at the NADPH binding site. The stoichiometric results with TNBS showed that 4 mol of lysine residues are modified per mole of fatty acid synthetase upon complete inactivation. The rapid reaction of two amino groups per enzyme molecule led to the loss of 60% of the enzyme activity. These approaches suggested that two lysine residues present at the active site are essential for the enzymatic activity of fatty acid synthetase.
Animals↗
Hepatic fatty acid composition in periparturient dairy cows with fatty liver induced by intake of a high energy diet in the dry period.
The present study compared the hepatic fatty acid composition of cows that were fed a high energy diet during the dry period to induce fatty liver after parturition with that of control cows. Treated cows had higher concentrations of plasma nonesterified fatty acids as a result of greater lipolysis after parturition than did control cows; consequently, the treated cows accumulated greater amounts of triacylglycerols in the liver. Before parturition, treated cows had lower percentages of oleic acid and higher percentages of linoleic acid than did control cows, but percentages of other fatty acids were similar for both groups. After parturition, percentages of each fatty acid were changed substantially, particularly the four major fatty acids (palmitic, stearic, oleic, and linoleic acids). For treated cows, the percentages of palmitic and oleic acids were higher at 0.5 wk after parturition than at 1 wk before parturition; percentages of stearic and linoleic acids decreased. Unlike treated cows, the percentages of both oleic and linoleic acids in the control cows did not change during that time. Moreover, we found that when lipolysis decreased, as indicated by lower plasma nonesterified fatty acid concentrations, the percentages of each fatty acid gradually rebounded toward the concentrations measured before parturition; this observation indicates that the shift in hepatic fatty acid composition is influenced by lipolysis. The increased lipolysis after parturition led to a vast increase in the hepatic triacyglycerol concentration and to a shift in hepatic fatty acid composition.
3-Hydroxybutyric Acid↗
Effect of fatty liver on hepatic gluconeogenesis in periparturient dairy cows.
The purpose of this study was to compare the hepatic enzyme activities of gluconeogenesis between control cows and experimental cows that had been overfed during the dry period to induce fatty liver postpartum. Blood and liver samples were collected 1 wk before and 0.5, 1, 2, and 3 wk after parturition. Before parturition, neither the serum nonesterified fatty acid nor the liver triacylglycerol concentration differed between the two groups. After parturition, these variables were higher in experimental cows than in control cows. Liver glycogen was higher at 1 wk before parturition in experimental cows; sharply decreased after parturition in both groups; and, at 1 wk after parturition, was lower in experimental cows than in control cows. In the liver, activities of phosphoenolpyruvate carboxykinase were significantly lower at 1 wk before and at 0.5 and 2 wk after parturition in experimental cows; in addition, the activities tended to be lower at 1 wk after parturition. Activities of fructose 1,6-bisphosphatase tended to be lower, but activities of glucose 6-phosphatase tended to be higher, at 0.5 wk after parturition in experimental cows than in control cows. Our results suggest that, in fatty infiltrated liver, the rate of gluconeogenesis is not optimal, which results in prolongation of lipolysis, particularly during the first weeks after parturition.
Animals↗
Fluorescence studies of chicken liver fatty acid synthase. Segmental flexibility and distance measurements.
The 4'-phosphopantetheine of chicken liver fatty acid synthase was specifically labeled with the fluorescent substrate analog coenzyme A 6-[7-nitrobenz-2-oxa-1,3-diazol-4-yl]aminohexanoate at low salt concentrations. A serine at the active site of the thioesterase was specifically labeled with the fluorescent compounds 6-[7-nitrobenz-2-oxa-1,3-diazol-4-yl]aminopentylmethylphosphono fluoridate and/or pyrenebutyl methylphosphonofluoridate. Dynamic anisotropy measurements indicate the thioesterase has considerable segmental flexibility, whereas the fluorescent labeled 4'-phosphopantetheine does not display detectable local or segmental flexibility. Fluorescence resonance energy transfer measurements indicate that the distance between the fluorescent label at the end of the 4'-phosphopantetheine and NADPH bound to the beta-ketoacyl reductase or enoyl reductase site on the same polypeptide chain is essentially the same, approximately 38 A. The two types of reductases were distinguished by specifically blocking enoyl reductase with pyridoxal 5'-phosphate. No significant energy transfer occurs between sites on different polypeptide chains so that the distances must be greater than 55 A. The distance between the serine on the thioesterase and the 4'-phosphopantetheine on the same polypeptide is 48 A; again no interpolypeptide chain energy transfer was observed. The distance between the serines of the two thioesterases within a fatty acid synthase molecule is greater than 56 A. The monomeric enzyme obtained at 1 degree C does not have beta-ketoacyl synthase and reductase activities. Also fluorescent titrations indicate NADPH is not bound to beta-ketoacyl reductase in monomeric enzyme. The addition of potassium phosphate to the monomers at 1 degree C rapidly dimerizes the enzyme and restores the beta-ketoacyl reductase activity. The beta-ketoacyl synthase activity is slowly restored when the dimer is raised to room temperature. The results obtained suggest that relatively large conformational changes may be part of the catalytic cycle.
3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗
Nonalcoholic fatty liver disease: implications for alcoholic liver disease pathogenesis.
This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The presentation was Nonalcoholic fatty liver disease: Implications for alcoholic liver disease pathogenesis, by Anna Mae Diehl.
Animals↗
Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition?
It is not known whether obesity increases the risk for hepatocellular carcinoma (HCC) simply because it promotes cirrhosis, a general risk factor for HCC, or via some other mechanism that operates independently of cirrhosis. If the latter occurs, then hepatocyte hyperplasia, an early event during the neoplastic process, might begin before liver cirrhosis develops. Genetically obese, leptin-deficient ob/ob mice are models for nonalcoholic fatty liver disease (NAFLD), a type of liver disease that is strongly associated with obesity and type 2 diabetes. Similar to obese, diabetic patients, ob/ob mice have an increased incidence of HCC. However, unlike humans with NAFLD, they rarely, if ever, develop cirrhosis spontaneously. To determine whether the noncirrhotic livers of ob/ob mice with NAFLD exhibit hepatocyte hyperplasia, parameters of proliferation and apoptosis were compared in adult ob/ob mice and their healthy litter mates. Adult ob/ob mice have an increase in liver mass relative to body mass. This hepatomegaly cannot be explained solely by lipid accumulation and is accompanied by significant increases in hepatocyte proliferative activity (as evidenced by increased Erk activation, cell-cycle related gene expression, bromodeoxyuridine incorporation, and hepatic DNA content) with concomitant inhibition of hepatocyte apoptosis (as evidenced by decreased numbers of apoptotic hepatocytes, induction of several antiapoptotic mechanisms, and decreased activation of procaspase 3). Thus, liver hyperplasia is evident at the earliest stage of NAFLD in ob/ob mice, which supports the concept that obesity-related metabolic abnormalities, rather than cirrhosis, initiate the hepatic neoplastic process during obesity.
Animals↗
[Effects of intravascular contrast media on urinary excretion of liver fatty acid-binding protein].
Proximal tubules of the kidney produce liver fatty acid-binding protein (L-FABP) and the level of messenger RNA is increased by physical and chemical stimuli. In this study, changes in urinary excretion of L-FABP were examined in 18 patients without renal dysfunction and who had undergone angiography using iodinated contrast media. On the day following angiography, the urinary excretion of L-FABP was markedly increased by 578 % (p<0.001) as compared with the value before the administration of contrast media. The urinary N-acetyl-beta-D-glucosaminidase excretion was also increased by +93%, however, the extent was less marked than for L-FABP. The urinary L-FABP excretion swiftly returned to the basal level on the second day after the angiography. No patient showed an increase in serum creatinine concentration, and the changes in urinary excretions of other microproteins, such as beta2-microglobulin and alpha1-microglobulin, were not significant. These results suggest that the urinary excretion of L-FABP sensitively reflects the injurious stress on renal tubules. Monitoring of urinary L-FABP may be useful in detecting the development of contrast media nephropathy at an early stage.
Acetylglucosaminidase↗
Comparison of the coagulation profile of fatty liver haemorrhagic syndrome-susceptible laying hens and normal laying hens.
1. The rate of thrombin generation in plasma from Fatty Liver Haemorrhagic Syndrome-susceptible laying hens (FLHS, UCD-003) is more rapid than in plasma from age-matched normal Single Comb White Leghorn (SCWL) laying hens. 2. The rate of thrombin generation in plasma was determined by measuring the biological activity of the specific coagulation proteins, Factors V, VII, VIII, IX and X. 3. The higher activity of Factors V, VII and X in FLHS-susceptible laying hens compared with normal SCWL hens remained consistent after plasma lipid concentrations were reduced. 4. Analysis of the fatty acid composition of plasma phospholipids showed that in normal SCWL laying hens phosphatidylethanolamine contained C18:3n3 whereas it contained C20:3n3 in FLHS-susceptible laying hens. 5. The results suggest that alterations in the composition of the phospholipids that are essential cofactors in the biochemical reactions involved in thrombin generation may be a contributing factor in the development of FLHS.
Animals↗
Focal fatty liver change in a 12-year-old Japanese boy.
We describe a 12-year-old patient with focal fatty liver change (FFLC). The lesion was incidentally detected by ultrasonography which showed a circumscribed hyperechoic lesion measuring approximately 6 x 4 cm. The lesion was also examined by CT and MRI. Histologically, the lesion corresponded to a focal area of lipid-laden hepatocytes. FFLC has been delineated as a disease entity in adults. As shown by this report, it may also occur in children. There was no associated clinical morbidity and the lesion was incidentally detected by modern imaging techniques. The aetiology and pathogenesis are unknown. The significance of focal fatty lesions is their differentiation from other focal lesions such as hepatic cell carcinomas, metastatic tumours, abscess and benign tumours including lipoma, haemangioma and angiomyolipoma.
Child↗
Non-alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects.
BACKGROUND/AIMS: Studies on non-alcoholic fatty liver disease (NAFLD) have included chronic liver damage attributed to various causes. Our investigation was held to observe the main clinical, histological, and pathophysiological aspects of NAFLD in patients not exposed to any known cause of chronic liver disease. METHODS: We evaluated, in 84 in-patients (male/female, 66/18; median age, 36 years), the clinical and biochemical characteristics of NAFLD, and particularly its association with diabetes, dyslipidemia, hyperinsulinemia and/or with the increase of parameters of oxidative stress (blood levels of malonyldialdehyde, 4-hydroxynonenal and total plasma antioxidant capacity). RESULTS: Ninety percent of patients had an increased body mass index (BMI), 35% had dyslipidemia, 40% had sub-clinical diabetes (only 3% had overt diabetes), 60% had hyperinsulinemia, and more than 90% had enhanced levels of lipid peroxidation markers. In 48 patients who had consented to liver biopsy, we found: 14 with simple steatosis, 32 with steatohepatitis, and two with cirrhosis. CONCLUSIONS: Our data indicate that in our country, NAFLD may occur in young males with an increased BMI, with or without hyperinsulinemia, dyslipidemia and diabetes, generally associated with disorders of redox status, and that it may be differentiated from steatosis to steatohepatitis or cirrhosis only with a liver biopsy.
Adolescent↗
Metabolic changes associated with the occurrence of fatty liver and kidney syndrome in chicks.
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.
Animals↗
Histologic variation of grade and stage of non-alcoholic fatty liver disease in liver biopsies.
BACKGROUND: Sampling error regarding disease grade and stage has been ascribed to needle liver biopsies in patients with chronic liver disease. Although several studies evaluating sampling error in liver biopsies exist, none have investigated this phenomenon in patients with non-alcoholic fatty liver disease (NAFLD). This study aims to determine the rate and extent of sampling error in liver biopsies obtained from patients undergoing Roux-en-Y gastric bypass (RYGBP) surgery for morbid obesity. METHODS: 10 morbidly obese patients underwent simultaneous liver biopsies from the right and left hepatic lobes during an open examination preceding the RYGBP procedure. The biopsies were subsequently randomly evaluated and then blindly re-evaluated by a liver pathologist. Degrees of inflammatory activity and fibrosis were determined and scored for each sample using a semi-quantitative system with 3 grades and 4 stages. RESULTS: No grading differences were observed, and 3 patients (30%) had a difference of at least 1 stage between the right and left lobes. One patient had a 2-stage difference in paired samples, with significantly different biopsy sizes and number of portal tracts. Blinded histologic re-evaluation did not result in grading or staging scores that differed from the original evaluation. CONCLUSIONS: Liver biopsy samples taken from the right and left hepatic lobes showed similar grades of disease activity, but differed in histopathologic staging in 30% of the NAFLD patients. Obtaining an adequately sized biopsy (>1.0 cm in length with >10 portal tracts) greatly reduces sampling error.
Adult↗