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)

There are limited data on nonalcoholic fatty liver disease (NAFLD) from India. The clinicopathological profile of Indian patients with NAFLD may be different from that of Western patients. One hundred NAFLD patients with increased liver enzymes were prospectively evaluated for clinical presentation, associated diseases, overweight/obesity, central obesity (n=54), presence of diabetes mellitus, lipid abnormalities, insulin resistance (n=39), metabolic syndrome (n=54), serum iron, serum ferritin, and transferrin saturation (n=60), and HFE gene mutations (n=30). Risk factors for the grade and stage of the disease on histology were studied in 38 biopsy-proven patients. Patients were treated with lifestyle modifications and ursodeoxycholic acid (UDCA). Seventeen nonresponder patients were treated with metformin. The majority of patients were males (n=70). Twenty percent of patients were overweight, 68% had obesity, and 78% had central obesity. Abnormal cholesterol, HDL, and triglycerides were present in 36%, 66%, and 53% of patients, respectively. Twelve percent of patients had diabetes mellitus and 16% patients had various associated diseases. All 22 (100%) patients studied by ITT and all but 1 (98%) studied by HOMA-IR were found to have reduced insulin sensitivity and 50% were found to have metabolic syndrome by the modified ATP III criteria. Two (3%) patients were found to have high serum iron, 4 (7%) patients had high ferritin, 5 (8%) patients had increased transferrin saturation, and 4 (13%) patients were found to be heterozygotes for H63D HFE gene mutation. Twenty patients of 38 (53%) had histological evidence of NASH (class 3=6, class 4=14). The other 18 (47%) qualified for class I (n=1) or class II (n=17) NAFLD. Four (10.5%) patients had bridging fibrosis and none had evidence of cirrhosis liver. Seventy-four (74%) patients achieved a biochemical response to lifestyle modification and UDCA. All 17 patients treated with metformin had a reduction in ALT level and 10 (59%) of them had normalization of their enzymes. We conclude that the clinicopathological profile of NAFLD in Indian patients is different from that in the West.
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PMID:The clinicopathological profile of Indian patients with nonalcoholic fatty liver disease (NAFLD) is different from that in the West. 1742 Sep 51

The mechanisms by which ethanol consumption causes accumulation of hepatic triacylglycerols are complex. AMP-activated protein kinase (AMPK) plays a central role in the regulation of lipid metabolism. Therefore, in the present study we investigated whether AMPK may have a role in the development of ethanol-induced fatty liver. Hepatocytes isolated from rats fed with an ethanol-containing liquid diet showed higher rates of fatty acid and triacylglycerol syntheses, but a decreased rate of fatty acid oxidation, concomitant to a lower activity of carnitine palmitoyltransferase I. Hepatocytes from both ethanol-fed and pair-fed control rats were incubated with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), an AMPK activator in intact cells. In both hepatocyte preparations AICAR strongly inhibited the activity of acetyl-CoA carboxylase in parallel to fatty acid synthesis, but cells from ethanol-fed rats showed significantly lower sensitivity to inhibition by AICAR. Moreover, AICAR strongly decreased triacylglycerol synthesis and increased fatty acid oxidation in control hepatocytes, but these effects were markedly attenuated in hepatocytes from ethanol-fed rats. In parallel, AMPK in liver of ethanol-fed rats showed a decreased specific activity and a lower sensitivity to changes in the AMP/ATP ratio, compared to the enzyme of control rats. These effects are consistent with the impairment of AMPK-mediated regulation of fatty acid metabolism after ethanol consumption, that will facilitate triacylglycerol accumulation. Taken together, these findings suggest that a decreased AMPK activity may have an important role in the development of alcoholic fatty liver.
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PMID:Ethanol consumption impairs regulation of fatty acid metabolism by decreasing the activity of AMP-activated protein kinase in rat liver. 1799 5

Non-alcoholic steatohepatitis (NASH) is an increasing recognized condition that may progress to end-stage liver disease. There are consistent evidences that mitochondrial dysfunction plays a central role in NASH whatever its origin. Mitochondria are the key controller of fatty acids removal and this is part of an intensive gene program that modifies hepatocytes to counteract the excessive fat storage. Mitochondrial dysfunction participates at different levels in NASH pathogenesis since it impairs fatty liver homeostasis and induces overproduction of ROS that in turn trigger lipid peroxidation, cytokines release and cell death. In this review we briefly recall the role of mitochondria in fat metabolism and energy homeostasis and focus on the role of mitochondrial impairment and uncoupling proteins in the pathophysiology of NASH progression. We suggest that mitochondrial respiratory chain, UCP2 and redox balance cooperate in a common pathway that permits to set down the mitochondrial redox pressure, limits the risk of oxidative damage, and allows the maximal rate of fat removal. When the environmental conditions change and high energy supply occurs, hepatocytes are unable to replace their ATP store and steatosis progress to NASH and cirrhosis. The beneficial effects of some drugs on mitochondrial function are also discussed.
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PMID:Mitochondrial involvement in non-alcoholic steatohepatitis. 1806 59

The adenine monophosphate (AMP) activated protein kinase (AMPK), is a heterotrimeric complex that is activated by an increase in the AMP/ATP ratio, and is considered to be a cellular energy sensor that contributes to regulate energy balance and caloric intake. AMPK is activated by LKB1 hinase and it can phophorylate several enzymes involved in anabolism to prevent further ATP consumption, and induces some catabolic enzymes to increase ATP generation. Furthermore, AMPK regulates the expression of genes involved in lipogenesis and mitochondrial biogenesis, among others. AMPK is distributed in most organs including, liver, skeletal muscle, heart and hypothalamus; and even in adipose cells. In addition, AMPK is activated in the hypothalamus stimulating appetite due to energy depletion. AMPK also participates in glycolysis regulation, glucose uptake, lipid oxidation, fatty acid synthesis, cholesterol synthesis and gluconeogenesis, and it has been considered as a possible target enzyme in the treatment of some diseases such as obesity, type 2 diabetes and hepatic steatosis. This review provides a general overview of AMPK structure, its activators and its function in the organism.
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PMID:[AMPK as a cellular energy sensor and its function in the organism]. 1840 38

The relationship between insulin resistance and mitochondrial function is of increasing interest. Studies looking for such interactions are usually made in muscle and only a few studies have been done in liver, which is known to be a crucial partner in whole body insulin action. Recent studies have revealed a similar mechanism to that of muscle for fat-induced insulin resistance in liver. However, the exact mechanism of lipid metabolites accumulation in liver leading to insulin resistance is far from being elucidated. One of the hypothetical mechanisms for liver steatosis development is an impairment of mitochondrial function. We examined mitochondrial function in fatty liver and insulin resistance state using isolated mitochondria from obese Zucker rats. We determined the relationship between ATP synthesis and oxygen consumption as well as the relationship between mitochondrial membrane potential and oxygen consumption. In order to evaluate the quantity of mitochondria and the oxidative capacity we measured citrate synthase and cytochrome c oxidase activities. Results showed that despite significant fatty liver and hyperinsulinemia, isolated liver mitochondria from obese Zucker rats display no difference in oxygen consumption, ATP synthesis, and membrane potential compared with lean Zucker rats. There was no difference in citrate synthase and cytochrome c oxidase activities between obese and lean Zucker rats in isolated mitochondria as well as in liver homogenate, indicating a similar relative amount of hepatic mitochondria and a similar oxidative capacity. Adiponectin, which is involved in bioenergetic homeostasis, was increased two-fold in obese Zucker rats despite insulin resistance. In conclusion, isolated liver mitochondria from lean and obese insulin-resistant Zucker rats showed strictly the same mitochondrial function. It remains to be elucidated whether adiponectin increase is involved in these results.
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PMID:Fatty liver and insulin resistance in obese Zucker rats: no role for mitochondrial dysfunction. 1853 99

The aim of this study is to investigate the respective associations of alanine aminotransferase (ALT), white blood cell (WBC) count, and uric acid with metabolic syndrome and compare the magnitude in their association with metabolic syndrome, using modified Adult Treatment Panel III (ATP III) and its components. We studies 5,020 Korean adults (20-70 years of age; 2,501 men and 2,519 women) who visited Center for Health Promotion in Pusan National University Hospital for routine health examinations. Metabolic parameters and biochemical markers including ALT, WBC count, and uric acid were obtained. Alcohol intake, smoking status, and the presence of fatty liver were also evaluated. The prevalence of metabolic syndrome was 17.3%. In the partial correlation coefficients adjusted for age, alcohol consumption, smoking status, and presence of fatty liver, ALT was correlated significantly with all components of metabolic syndrome among three markers in men and women respectively. Moreover, ALT showed the highest correlation with HOMA-IR (r=0.311, P<0.001 in men and r=0.285, P<0.001 in women) in both genders. With the increase in the number of metabolic syndrome components, the mean values of all three markers were also significantly increased. In addition, the adjusted mean values of each marker were all significantly increased in metabolic syndrome. In ALT, the adjusted mean values were significantly increased in subjects with all metabolic component disorders. When we calculated odd ratios (ORs) for metabolic syndrome prevalence of the highest quartiles in three markers using multivariate logistic regression analyses, ALT was associated most strongly with metabolic syndrome in both genders (OR 5.65 [95% CI, 3.80 to 8.40]; P<0.001 in men, OR 3.23 [95% CI, 2.15 to 4.86]; P<0.001 in women). The cut-off value for ALT using the ROC curve was 27 IU/L (area under the curve=0.717, sensitivity 62.5%, specificity 70.4%, P<0.001) in men and 18 IU/L (area under the curve=0.735, sensitivity 61.3%, specificity 72.3%, P<0.001) in women. In conclusion, ALT, WBC count, and uric acid play important role as an additional markers for metabolic syndrome. Among three markers, in overlap the multiple risk factors, ALT might have a strong association with metabolic syndrome in Korean adults.
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PMID:Comparison of alanine aminotransferase, white blood cell count, and uric acid in their association with metabolic syndrome: a study of Korean adults. 1875 5

The effect of target-directed regulation of the uncoupling protein-2 (UCP-2) gene expression on the ischemia-reperfusion injury of hepatocytes under different conditions was investigated. The expression plasmid and RNAi plasmid targeting UCP-2 gene were constructed and transfected into normal hepatocytes and fatty liver cells, respectively. The expression of UCP-2 mRNA was detected by real time PCR. The cells were divided into normal cell group (NCG), group of normal cells transfected with empty vector (EVNCG), group of normal cells transfected with expression plasmid (EPNCG), fatty liver cell group (FCG) and group of fatty liver cells transfected with RNAi plasmid (RPFCG). The ischemia-reperfusion model in vitro was established. One, 6, 12 and 24 h after reperfusion, Annexin V/PI flow cytometry was used to measure cell necrosis rate, apoptosis rate and survival rate. Simultaneously, the intracellular ATP, ROS and MDA levels were determined. The results showed that 1, 6, 12 and 24 h after ischemia-reperfusion, the intracellular ROS, MDA and ATP levels and cell survival rate in EPNCG were significantly lower, and cell necrosis rate significantly higher than in NCG and EVNCG, but there was no significant difference in apoptosis rate among NCG, EVNCG and EPNCG (P>005). Six, 12 and 24 h after reperfusion there was no significant difference in ROS, MDA levels and apoptosis rate between FCG and RPFCG (P>0.05), but the ATP level and survival rate of cells in RPFCG were higher than in FCG (P<0.05). It was concluded that down-regulation of the UCP-2 gene expression in steatotic hepatocytes could alleviate the ischemia-reperfusion injury of liver cells.
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PMID:Effect of target-directed regulation of uncoupling protein-2 gene expression on ischemia-reperfusion injury of hepatocytes. 1884 38

The medaka fish (Oryzias latipes) is an emerging model organism for which a variety of unique developmental mutants have now been generated. Our recent mutagenesis screening of the medaka isolated a unique mutant that develops a fatty liver at larval stages. Positional cloning identified the responsible gene as medaka abcb7. Abcb7, a mitochondrial ABC (ATP binding cassette) half-transporter, has been implicated in iron metabolism. Recently, human Abcb7 was found to be mutated in X-linked sideroblastic anemia with cerebellar ataxia (XLSA/A). The homozygous medaka mutant exhibits abnormal iron metabolism in erythrocytes and accumulation of lipid in the liver. Microarray and in situ hybridization analyses demonstrated that the expression of genes involved in iron and lipid metabolisms are both affected in the mutant liver, suggesting novel roles of Abcb7 in the development of physiologically functional liver. The medaka abcb7 mutant thus could provide insights into the pathogenesis of XLSA/A as well as the normal function of the gene.
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PMID:Mutation in the abcb7 gene causes abnormal iron and fatty acid metabolism in developing medaka fish. 1904 59

As the liver is central in the maintenance of glucose homeostasis and energy storage, knowledge of the physiology as well as physiopathology of hepatic energy metabolism is a prerequisite to our understanding of whole-body metabolism. Hepatic fuel metabolism changes considerably depending on physiological circumstances (fed vs. fasted state). In consequence, hepatic carbohydrate, lipid and protein synthesis/utilization are tightly regulated according to needs. Fatty liver and hepatic insulin resistance (both frequently associated with the metabolic syndrome) or increased hepatic glucose production (as observed in type 2 diabetes) resulted from alterations in substrates oxidation/storage balance in the liver. Because AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor, it is important to gain understanding of the mechanism by which hepatic AMPK coordinates hepatic energy metabolism. AMPK has been implicated as a key regulator of physiological energy dynamics by limiting anabolic pathways (to prevent further ATP consumption) and by facilitating catabolic pathways (to increase ATP generation). Activation of hepatic AMPK leads to increased fatty acid oxidation and simultaneously inhibition of hepatic lipogenesis, cholesterol synthesis and glucose production. In addition to a short-term effect on specific enzymes, AMPK also modulates the transcription of genes involved in lipogenesis and mitochondrial biogenesis. The identification of AMPK targets in hepatic metabolism should be useful in developing treatments to reverse metabolic abnormalities of type 2 diabetes and the metabolic syndrome.
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PMID:AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives. 1924 56

Since its first description by Reavan in 1988, accepted criteria for clinical identification of the components of metabolic syndrome have been promulgated by the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) and the World Health Organization (WHO) as well as the International Diabetes Federation (IDF), and the American Association of Clinical Endocrinologists (AACE). Insulin resistance is a common metabolic abnormality underlying type 2 diabetes mellitus and is also an independent risk factor for cardiovascular disease. Although ATP III identified cardiovascular disease (CVD) as the primary clinical outcome of the metabolic syndrome, we now have evidence that metabolic syndrome is associated with type 2 diabetes mellitus, polycystic ovarian disease, nonalcoholic fatty liver disease, and possibly some cancers. This review summarizes evidence in support of the relationship between metabolic syndrome and various cancers and possible underlying mechanisms and therapeutic interventions.
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PMID:Metabolic syndrome and cancer. 1928 14


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