UMLS:C0015695 - FACTA Search

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Query: UMLS:C0015695 (fatty liver)
13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoids, which are well established to regulate body fat mass distribution, adipocyte lipolysis, hepatic gluconeogenesis, and hepatocyte VLDL secretion, are speculated to play a role in the pathology of metabolic syndrome. Recent focus has been on the activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which is capable of regenerating, and thus amplifying, glucocorticoids in key metabolic tissues such as liver and adipose tissue. To determine the effects of global 11beta-HSD1 inhibition on metabolic syndrome risk factors, we subcutaneously injected "Western"-type diet-fed hyperlipidemic mice displaying moderate or severe obesity [LDL receptor (LDLR)-deficient (LDLR(-/-)) mice and mice derived from heterozygous agouti (A(y)/a) and homozygous LDLR(-/-) breeding pairs (A(y)/a;LDLR(-/-) mice)] with the nonselective 11beta-HSD inhibitor carbenoxolone for 4 wk. Body composition throughout the study, end-point fasting plasma, and extent of hepatic steatosis and atherosclerosis were assessed. This route of treatment led to detection of high levels of carbenoxolone in liver and fat and resulted in decreased weight gain due to reduced body fat mass in both mouse models. However, only A(y)/a;LDLR(-/-) mice showed an effect of 11beta-HSD1 inhibition on fasting insulin and plasma lipids, coincident with a reduction in VLDL due to mildly increased VLDL clearance and dramatically decreased hepatic triglyceride production. A(y)/a;LDLR(-/-) mice also showed a greater effect of the drug on reducing atherosclerotic lesion formation. These findings indicate that subcutaneous injection of an 11beta-HSD1 inhibitor allows for the targeting of the enzyme in not only liver, but also adipose tissue, and attenuates many metabolic syndrome risk factors, with more pronounced effects in cases of severe obesity and hyperlipidemia.
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PMID:Carbenoxolone treatment attenuates symptoms of metabolic syndrome and atherogenesis in obese, hyperlipidemic mice. 1787 20

The purpose of this study was to perform a comprehensive analysis of hepatic gene expression in a standard model of an alcohol-induced fatty liver using the cDNA microarray analysis. Male Sprague-Dawley rats were randomly divided into two groups and were given either an ethanol diet (ED), or a control diet (CD) for eight weeks. The ED rats showed significantly elevated levels of plasma total and HDL cholesterol as well as hepatic cholesterol and triglyceride compared to the pair-fed control rats. Among the 5185 genes on the rat cDNA microarray used in the current study, 74 genes were up-regulated and 108 genes were down-regulated greater than 2.0-fold in the liver of ED rats compared with those in the CD rats. The microarray results were verified by conducting real-time RT-PCR on the fourteen selected genes with varied expression ratios. After clustering the regulated genes based on their biological function, it was found that chronic ethanol consumption regulated mainly the genes implicated in the processes of signal transduction, transcription, immune response, and protein/amino acid metabolism. The microarray results obtained in this study revealed, for the first time, that several genes, including beta-glucuronidase, UDP-glycosyltransferase 1, UDP-glucose dehydrogenase, apoC-III, and gonadotropin-releasing hormone receptor, were regulated by chronic ethanol exposure in the rat liver.
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PMID:Changes in the hepatic gene expression profile in a rat model of chronic ethanol treatment. 1792 Jul 46

The objective of this work was to study the influence of insulin resistance and adipokines on the grade of steatosis in patients with NAFLD (nonalcoholic fatty liver disease) diagnosed by liver biopsy. A sample of 24 NAFLD patients was analyzed in a cross-sectional study. All patients with a two-week weight-stabilization period before recruitment were enrolled. A liver biopsy was realized. Weight, basal glucose, insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and adipokines blood levels were measured. A nutritional evaluation (dietary intake, indirect calorimetry, and bioimpedance) was performed. The mean age was 41.6 +/- 8.7 years and the mean body mass index (BMI) 29.4 +/- 4.7. Twelve patients had a low grade of steatosis (grade 1 of the Brunt classification) and 12 patients had a high grade of steatosis (grade 2 or 3). Only HOMA was higher in patients with a high grade of steatosis (1.4 +/- 0.5 vs. 2.8 +/- 1.7 units; P < 0.05). Anthropometric data and dietary intake were similar for both groups. Blood levels of adiponectin were higher in patients with a low grade of steatosis (37.7 +/- 22.5 vs. 24.2 +/- 33 ng mL(-1); P < 0.05). Blood levels of resistin were higher in patients with a high grade of steatosis (2.36 +/- 0.6 vs. 2.8 +/- 0.6 mg mL(-1); P < 0.05), without differences in TNF-alpha or leptin levels. In logistic regression analysis, the HOMA-IR remained in the model, with an odds ratio to develop high grade of steatosis of 7.8 (95% CI: 1.8-75) with each 1 unit of HOMA-IR adjusted by age, sex, BMI, and dietary intake. This study demonstrates that insulin resistance determined with the HOMA model is associated with a high grade of steatosis in patients with NAFLD.
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PMID:Influence of insulin resistance and adipokines in the grade of steatosis of nonalcoholic fatty liver disease. 1793 20

Evidence has been provided that increased levels of non esterified fatty acids (NEFA) in the portal flow would produce insulin resistance and would also stimulate the hepatic protein synthesis, thereby explaining the increased plasma levels not only of apolipoprotein B, but also of other liver-derived enzymes and proteins occurring in overweight and hypertriglyceridemic patients. The high plasma concentration of triglyceride-rich lipoprotein would facilitate the transfer of cholesteryl esters from HDL and LDL to VLDL in exchange for triglycerides, a process mediated by liver-derived cholesteryl ester transfer protein (CETP). The triglyceride thereby acquired in HDL and LDL would then be hydrolyzed by hepatic lipase. The resulting association of increased triglycerides, low HDL cholesterol and small dense LDL is considered to be an atherogenic profile. The prothrombotic state, another feature of the metabolic syndrome, may also be explained by an enhanced hepatic synthesis of clotting factors and of the inhibitors of fibrinolysis. It was recently shown that adipocyte synthesized adiponectin reduces the release of fatty acids from the adipose tissue and would also enhance their uptake and oxidation in the muscle, thereby limiting their uptake in the liver. Decreased adiponectin production in obesity would therefore promote the development of insulin resistance, of atherogenic dyslipidemia and of the prothrombotic state. Because adiponectin also exerts an antiinflammatory activity by antagonizing TNFalpha, hypoadiponectinemia may be involved in atherogenesis and in the progression of hepatic steatosis to steatohepatitis.
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PMID:Pathogenic role of abnormal fatty acids and adipokines in the portal flow. Relevance for metabolic syndrome, hepatic steatosis and steatohepatitis. 1833 68

There has been increasing number of obese children who accompany obesity-related comorbidities. It has been known that nonalcoholic fatty liver disease (NAFLD) as one of obesity-related comorbidities is related with insulin resistance. So, we investigated the relation between insulin resistance and NAFLD, using serum alanine aminotransferase (ALT) as a surrogate of NAFLD among obese children in Korea. The study subjects were 909 obese children aged 9-12 years (boys 613, girls 296). Body mass index (BMI), waist circumference (WC), blood pressure, fasting blood glucose, fasting insulin, lipid profile were measured. ALT, liver enzyme was used as a surrogate of NAFLD and homeostasis model assessment of insulin resistance (HOMA-IR) was used as the index of insulin resistance. The prevalence of elevated serum ALT (>or=40 mg/dl) was 33.4% in boys, and 19.6% in girls respectively. In boys, ALT was correlated with BMI, waist circumference, total cholesterol, triglyceride, HDL-cholesterol, systolic and diastolic blood pressure, HOMA-IR, fasting serum insulin. Odds ratio for HOMA-IR against the elevated ALT (>or=40 mg/dl) was 1.061 (95% confidence interval, 1.020-1.103, P=0.003). In girls, ALT was correlated with BMI, waist circumference, total cholesterol, triglyceride, glucose, systolic and diastolic blood pressure, HOMA-IR, fasting serum insulin. Odds ratio for HOMA-IR against the elevated ALT (>or=40 mg/dl) was 1.042 (95% confidence interval, 0.998-1.088, P=0.063). Among obese Korean children, insulin resistance and ALT, lipid profile, BMI, WC, blood pressure showed significant correlation. Especially, in boys, higher ALT is founded to be independently associated with insulin resistance.
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PMID:Relationship between insulin resistance and serum alanine aminotransferase as a surrogate of NAFLD (nonalcoholic fatty liver disease) in obese Korean children. 1857 Dec 68

Hepatic steatosis may develop secondary to abnormalities in lipid and/or glucose metabolism. We presume that a phenotype of lipid profile may represent pathogenetic variant of steatosis. liver steatosis had been diagnosed on ultrasonography in 108 patients (27 with alcoholic liver disease, 28 with chronic HCV hepatitis and 21 with chronic HBV hepatitis; 34 patients with chronic viral hepatitis (CVH) had alcohol abuse). Serum levels of total cholesterol (TC), its fractions and triglycerides (TG) were assessed by standard tests. chi2 (chi-square) criterion was used to assess reliability of the lipid parameters deviation, alcohol-induced (AI), virus-induced (VI) and mixed pathogenetic variants of liver steatosis had been identified. TC level >200 mg/dL, LDL-cholesterol >120 mg/dL, TG >150 mg/dL, and normo- or hypoglycemia were typical, while TC level<180 mg/dL and hyperglycemia were not found in patients with AI steatosis. TC level<180 mg/dL, LDL-cholesterol<100 mg/dL and TG<150 mg/dL were typical for VI steatosis. 46,4% of patients with HCV hepatitis and 19% of patients with HBV hepatitis had TC level<140 mg/dL and LDL-cholesterol<70 mg/dL. In patients with CVH and alcohol abuse a mixed variant of liver steatosis has been diagnosed, their serum lipid levels were lower than those in patients with alcoholic liver disease, and insignificantly higher than those in patients with CVH. Conclusions. Determination of pathogenetic type of steatosis in patients with fatty infiltration of the liver is adjunctive to the diagnosis and is a screening test for patients with CVH. Serum levels of HDL-cholesterol below normal values were frequently seen in patient with III grade steatosis.
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PMID:[Pathogenetic variants of liver steatosis: diagnostic approach using serum lipid levels]. 1882 48

Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD). Several studies pointed out the possible role of increased leptin in NAFLD in humans. The aim of this study is to determine the effect of metformin on plasma leptin levels in obese patients with type 2 diabetes mellitus and NAFLD compared with lifestyle interventions. Thirty-four obese patients with newly diagnosed type 2 diabetes mellitus were prospectively followed for 6 months. All patients had ultrasonographic evidence of NAFLD at baseline. The patients were randomized into two groups: group 1 (n = 15) followed lifestyle changes only and group 2 (n = 19) received metformin (1,700 mg/day). At the end of treatment, BMI, WHR, HbA1c, fasting glucose, leptin, HOMA-IR, alanine aminotransferase values decreased in both groups. No significant difference in the end-points was observed between two groups. Only in group 2, LDL decreased and HDL increased significantly. Liver echogenity decreased significantly at the end of study in both groups. The percentage of patients who no longer had evidence of NAFLD was not significantly different between the groups (20% of patients on lifestyle intervention vs. 16% of patients on metformin). The data demonstrate that, metformin and lifestyle interventions equally affected the plasma leptin levels, BMI and degree of NAFLD in obese patients with type 2 diabetes mellitus. In addition, the effects of metformin on the variables were not found to be mediated by leptin.
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PMID:The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. 1883 53

The effects of dietary monosodium glutamate (MSG) on trans-fatty acid (TFA)-induced nonalcoholic fatty liver disease (NAFLD) are addressed in an animal model. We used Affymetrix microarray analysis to investigate hepatic gene expression and the contribution of visceral white adipose tissue (WAT) to diet-induced NAFLD. Trans-fat feeding increased serum leptin, FFA, HDL-cholesterol (HDL-C), and total cholesterol (T-CHOL) levels, while robustly elevating the expression of genes involved in hepatic lipogenesis, including the transcription factor sterol-regulatory element binding protein 1c. Histological examination revealed hepatic macrosteatosis in TFA-fed animals. Conversely, dietary MSG at doses similar to human average daily intake caused hepatic microsteatosis and the expression of beta-oxidative genes. Serum triglyceride, FFA, and insulin levels were elevated in MSG-treated animals. The abdominal cavities of TFA- or MSG-treated animals had increased WAT deposition compared with controls. Microarray analysis of WAT gene expression revealed increased lipid biosynthetic gene expression, together with a 50% decrease in the key transcription factor Ppargc1a. A combination of TFA+MSG resulted in the highest levels of serum HDL-C, T-CHOL, and leptin. Microarray analysis of TFA+MSG-treated livers showed elevated expression of markers of hepatic inflammation, lipid storage, cell damage, and cell cycle impairment. TFA+MSG mice also had a high degree of WAT deposition and lipogenic gene expression. Levels of Ppargc1a were further reduced to 25% by TFA+MSG treatment. MSG exacerbates TFA-induced NAFLD.
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PMID:Effect of dietary monosodium glutamate on trans fat-induced nonalcoholic fatty liver disease. 1900 66

This cross sectional study evaluated serum (SMg) and intramononuclear (MMg) magnesium in patients with metabolic syndrome without diabetes and correlated them with cardiovascular risk factors. 72 patients and 57 controls (blood donors) were studied. Hypomagnesemia (SMg<1.7 mg/dL) was seen in 23.2% and intracellular depletion in 36.1% of the patients. SMg and MMg means were significantly lower in patients than in controls: 1.80+/-0.18 mg/dL vs. 2.43+/-0.43 mg/dL and 0.98+/-0.55 microg/mg vs. 1.67+/-0.64 microg/mg of protein (P<0.001). Inverse correlation was observed between, SMg and MMg with BMI; SMg with systolic blood pressure and waist circumference in women. Patients with acanthosis nigricans had lower SMg (1.75+/-0.18 mg/dL vs. 1.85+/- 0.18 mg/dL, P<0.05). Non-white people had lower SMg (1.78+/-0.16 mg/dL vs. 1.92+/-0.24 mg/dL, P=0.007) and MMg (0.95+/-0.59 microg/mg vs. 1.13+/-0.42 microg/mg, P=0.03). Patients with IR showed lower MgM means (0.84+/-0.33 microg/mg vs. 1.14+/-0.69 microg/mg, P<0.05). The same occurred in patients with low HDL-c levels (0.92+/-0.46 microg/mg vs. 1.20+/-0.70 microg/mg, P=0.03), and those with moderate and severe hepatic steatosis (0.77+/-0.29 microg/mg vs. 1.21+/-0.80 microg/mg, P<0.05). In conclusion, magnesium depletion in serum and mononuclear cells is common in obese people with metabolic syndrome, and it is more evident in non-white people with insulin resistance. This depletion may contribute to a post-receptor insulin resistance.
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PMID:Serum and intracellular magnesium deficiency in patients with metabolic syndrome--evidences for its relation to insulin resistance. 1912 69

Metabolic dyslipidemia is characterized by high circulating triglyceride (TG) and low HDL cholesterol levels and is frequently accompanied by hepatic steatosis. Increased hepatic lipogenesis contributes to both of these problems. Because insulin fails to suppress gluconeogenesis but continues to stimulate lipogenesis in both obese and lipodystrophic insulin-resistant mice, it has been proposed that a selective postreceptor defect in hepatic insulin action is central to the pathogenesis of fatty liver and hypertriglyceridemia in these mice. Here we show that humans with generalized insulin resistance caused by either mutations in the insulin receptor gene or inhibitory antibodies specific for the insulin receptor uniformly exhibited low serum TG and normal HDL cholesterol levels. This was due at least in part to surprisingly low rates of de novo lipogenesis and was associated with low liver fat content and the production of TG-depleted VLDL cholesterol particles. In contrast, humans with a selective postreceptor defect in AKT2 manifest increased lipogenesis, elevated liver fat content, TG-enriched VLDL, hypertriglyceridemia, and low HDL cholesterol levels. People with lipodystrophy, a disorder characterized by particularly severe insulin resistance and dyslipidemia, demonstrated similar abnormalities. Collectively these data from humans with molecularly characterized forms of insulin resistance suggest that partial postreceptor hepatic insulin resistance is a key element in the development of metabolic dyslipidemia and hepatic steatosis.
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PMID:Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. 1924 6

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