Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Few mutations have been found in the human leptin gene and the relationship between leptin gene sequence variation and human overweight is uncertain. To determine whether sequence variation within the leptin gene and its regulatory elements contribute to extreme obesity, we screened approximately 3 kb of the 5' flanking region and the three exons in 125 unrelated extremely obese (BMI > or = 40 kg/m2) and 86 average weight women (BMI < 27 kg/m2). Within the protein coding regions only one heterozygous silent mutation was found (codon 102; AAC/AAT). Within the 5' flanking region, six frequent sequence variants were detected (q > 0.10), and the allele frequencies of three of these variants differed between obese and average weight Caucasian women (+19, chi 2 = 4.46, p = 0.035; -1823, chi 2 = 4.36, p = 0.037; -2548, chi 2 = 5.73, p = 0.017). Nine infrequent sequence variants were detected (q < 0.05) but they did not occur more often among obese women compared with those of average-weight. For extremely obese women, three polymorphisms (+19, -188, and -633) predicted the degree of obesity. Allelic variants may influence the regulation of the leptin gene and thereby influence body weight, particularly among extremely obese women. However, given the low variability in coding regions and the high variability in the 5' flanking region, discerning the functional significance of each variant is likely to be difficult.
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PMID:Sequence variants in the 5' flanking region of the leptin gene are associated with obesity in women. 1073 35

Adiponectin, secreted specifically from adipocytes, is thought to play a key role in the metabolic syndrome. Plasma adiponectin concentrations were studied in 36 typical nonalcoholic fatty liver (NAFL) women which is commonly associated with the metabolic syndrome. They were diagnosed as NAFL by ultrasound brightness, slightly elevated serum ALT levels and the exclusion of history of alcohol abuse and other known liver diseases. Compared with 64 control women, NAFL had a significant increase in the variables of the metabolic syndrome, other hepatic enzymes and leptin levels, while a reduction in AST/ALT ratio and adiponectin before (mean +/- SE: 7.2 +/- 0.5 vs 9.0 +/- 0.4 microg/ml, p < 0.005) and after adjustment for body fat mass (0.24 +/- 0.02 vs 0.34 +/- 0.02, p < 0.0001), atherogenic Index [(total cholesterol - HDLC)/HDLC: 3.2 +/- 0.3 vs 4.6 +/- 0.3, p < 0.005] or calculated insulin resistance (HOMA-R) (6.6 +/- 1.9 vs 8.6 +/- 0.9, p < 0.005). BMI and amylase were positive, and adiponectin/BMI was negative significant independent determinants of ALT value in multiple regression model. In conclusion, while hypoadiponectinemia was observed in NAFL, hypoadiponectinemia provides the possibility of fat accumulation in the liver.
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PMID:Plasma adiponectin decrease in women with nonalcoholic Fatty liver. 1564 78

Severe lipodystrophy is characterized by diminished adipose tissue and hypoleptinemia, leading to ectopic triglyceride accumulation. In the liver, this is associated with steatosis, potentially leading to nonalcoholic steatohepatitis (NASH). We investigated the prevalence of NASH and the effect of leptin replacement in these patients. Ten patients with either generalized lipodystrophy (8 patients) or Dunnigan's partial lipodystrophy (2 patients) were included in this analysis. Paired liver biopsy specimens were obtained at baseline and after treatment with recombinant methionyl human leptin (r-metHuLeptin), mean duration 6.6 months. The extents of portal and parenchymal inflammation, steatosis, ballooning, presence of Mallory bodies, and fibrosis in liver biopsy specimens were scored using a previously validated system developed to assess NASH activity. Histological disease activity was defined as the sum of ballooning, steatosis, and parenchymal inflammation scores. We concurrently tested serum triglycerides and aminotransferases and estimations of liver volume and fat content by magnetic resonance imaging. Eight of 10 patients met histological criteria for NASH at baseline. After treatment with r-metHuLeptin, repeat histological examinations showed significant improvements in steatosis (P = .006) and ballooning injury (P = .005), with a reduction of mean NASH activity by 60% (P = .002). Fibrosis was unchanged. Significant reductions were seen in mean serum triglycerides (1206-->226 mg/dL, P = .002), glucose (220-->144 mg/dL, P = .02), insulin (46.4-->24.8 muIU/mL, P = .004), ALT (54-->24 U/L, P = .02), AST (47-->22 U/L, P = .046), liver volume (3209-->2391 cm(3), P = .007), and liver fat content (31-->11%, P = .006). In conclusion, r-metHuLeptin therapy significantly reduced triglycerides, transaminases, hepatomegaly, and liver fat content. These reductions were associated with significant reductions in steatosis and the hepatocellular ballooning injury seen in NASH.
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PMID:Leptin reverses nonalcoholic steatohepatitis in patients with severe lipodystrophy. 1579 19

Several studies have reported an association between markers of liver injury, including elevated concentrations of alanine aminotransferase (ALT) aspartate aminotransferase (AST), and prospective risk of type 2 diabetes. We therefore examined the relationship between ALT and AST on the one hand, and serum adiponectin and highly sensitive CRP on the other, both of which have been reported to be associated with prospective risk of type 2 diabetes; we also tested for variable components of metabolic syndrome in 198 male college students aged 18-20 years. ALT showed a positive relationship with percentage body fat (r = 0.19, p = 0.02), serum leptin (r = 0.21, p = 0.01), LDL cholesterol (r = 0.29, p = 0.0003), triglyceride (r = 0.28, p = 0.0004) and apolipoprotein B (r = 0.35, p < 0.0001) even after adjustment for body mass index (BMI). Although there was a significant relationship with serum insulin, adiponectin (inversely), homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure, HDL cholesterol (inversely) and LDL particle diameter in simple regression analysis, significance disappeared after adjustment for BMI. In contrast, CRP (r = 0.16, p = 0.04) was associated with ALT after adjustment for BMI, although simple regression analysis revealed no association between the two. Relationships were smaller for AST, and significance disappeared after adjustment for BMI. Multiple regression analysis excluding lipid variables revealed significant and independent associations of ALT with adiponectin and percentage body fat. In a model including lipid variables, apolipoprotein B emerged as an independent predictor of ALT in addition to adiponectin and percentage body fat. These variables explained 29 % of ALT variability. In conclusion, serum ALT levels were associated with leptin and CRP as well as many components of the insulin resistance syndrome in young healthy men. Adiponectin, apolipoprotein B and percentage body fat emerged as significant and independent predictors of ALT. Since adiponectin and chronic subclinical inflammation have been reported to predict the development of type 2 diabetes and since abnormalities in apolipoprotein B metabolism occur in the early course of insulin resistance, these findings may be compatible with the association between liver markers and risk of diabetes.
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PMID:Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men. 1652 13

The objectives of this research were to investigate the leptin levels among Chronic Hepatitis B Virus (HBV), Chronic Hepatitis C Virus (HCV) and non-alcoholic steatosis hepatitis (NASH) diseases of Thai patients compared with controls. Twenty of each HBV, HCV and NASH patients compared with sixty people as the control group from the Outpatient Department at the Hospital for Tropical Diseases, Bangkok, Thailand were investigated. Fasting blood samples were collected for investigation of leptin concentration, liver enzyme function tests and hematological variables. The serum leptin concentration of liver patients was significantly higher than that of control subjects. It might be due to the accumulations of fat cells in liver disease patients. However, there is no relationship between leptin level and other parameters such as BMI, ALT, AST, ALP and hematological variables. Liver enzyme functions levels are much higher in patients groups. White blood cells counts, platelets and hematocrit values are slightly lower in liver disease patients. Therefore, it is concluded that physiological regulation of leptin maintains in relation to body fat, even in chronic viral liver diseases. This finding and the apparent stage suggest the possibility that in the course of chronic viral diseases, serum leptin levels may reflect the extent of liver dysfunction.
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PMID:Serum leptin concentrations in chronic hepatitis. 1669 95

Ketosis was diagnosed in a flock of Merino ewes that conceived from synchronised oestrus in the early autumn period. On day 140 of pregnancy the ewes were sampled for determination of betaOH-butyrate (BHB), AST, glucose, non-esterified fatty acids (NEFA), total cholesterol (TCH), insulin, T4, T3, cortisol, IGF-1 and leptin. The results were evaluated according to the number of fetuses born some days later and the presence of hyperketonaemia (BHB: > or = 1.60 mmol/l). In May, about 3 months after lambing, cyclic ovarian function was induced (Cronolone + eCG), and the ewes were inseminated artificially (AI) 48 h after the removal of gestagen-containing sponge. At the time of AI and 10 days later blood samples were collected again to check the plasma levels of the same constituents as previously (in samples taken at AI), and to monitor the ovarian response by assaying progesterone (in both samples). On day 140 of gestation significantly lower BHB levels were detected in dams with single (n = 41) than in those with twin (n = 57) pregnancies. Hyperketonaemia was found only in ewes bearing twins (n = 27). These animals had higher NEFA and cortisol, and lower TCH, insulin, IGF-1, leptin and T3 levels than their normoketonaemic twin-bearing flock-mates, and those with single pregnancy. The blood glucose concentrations varied within a wide range, and the means of groups did not exhibit any significant differences. The formerly hyperketonaemic individuals were characterised by lower leptin level 3 months after lambing, and they showed a poorer response to the cycle-induction procedure than the others. The non-responders had lower IGF-1 and leptin levels than those ovulated after this treatment. It was concluded that the subclinical form of ovine ketosis is characterised by complex endocrine alterations, reflecting an obvious form of negative energy balance. If attempts to induce cyclic ovarian function outside the breeding season are made soon after lambing, the ovarian response and fertility of these ewes may also be depressed.
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PMID:Endocrine characteristics of late pregnant hyperketonaemic ewes and their reproductive performance following the induction of ovarian cyclicity out of the breeding season. 1684 61

Wersternized diet, containing high fat diet intake combined with high consumption of softdrinks, is accused with the emerge of modern epidemic obesity and diabesity. Therefore, we aimed to study the effect of this diet combination on the homeostasis of glucose, lipids, and some adipohormones in rats and to simulate the metabolic perturbations induced by the unhealthy Westernized diet intake, leading to the development of type 2 diabetes. To achieve this, we divided male Wistar rats (80-120 g) into two main groups: the first was fed commercial normal fat diet and the second received an in-house-prepared high-fat diet (HFD), combined with fructose in drinking water for a period of 6 weeks, followed by a subdiabetogenic dose of streptozotocin (STZ) (35 mg/kg) to produce frank hyperglycemia. The effect of this diet alone or after 2 weeks of treatment with rosiglitazone or glimepiride on glucose homeostasis, lipid profile, and levels of resistin and leptin was studied. The HFD/fructose/STZ diet elevated fasting plasma glucose, fructosamine, insulin, and homeostasis model assessment (HOMA) index, as well as serum triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol, with a decrease in high-density lipoprotein cholesterol. Hepatic TG and TC levels, as well as serum activities of aspartate transaminase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH), were increased, suggesting a diet-induced hepatic steatosis, beside the increased levels of serum resistin and leptin. Rosiglitazone corrected the altered parameters measured, except for liver TGs; similarly, glimepiride reinstated the inverted parameters but raised insulin level and, consequently, the HOMA index. These results show that this diet could be used to induce an effect that mimics human type 2 diabetes with its metabolic disturbances and is suitable for screening the antidiabetic agents used for management of this disease.
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PMID:Westernized-like-diet-fed rats: effect on glucose homeostasis, lipid profile, and adipocyte hormones and their modulation by rosiglitazone and glimepiride. 1840 27

Leptin is an adipocyte-secreted hormone which plays a key role in energy homeostasis. Our aim was to determine the relationship between serum leptin and clinical and biochemical features in overweight children and adolescents. Overweight children and adolescents followed in this Unit with serum leptin ascertained were included. Clinical, biochemical and abdominal ultrasound data were analysed. Statistical analysis was performed by t test, chi2, Pearson's correlation and linear regression. One outlier of serum leptin was excluded to perform correlation and regression. Serum leptin was determined in 357 patients. At the first visit, the mean age was 9.5 (sd 3.2) years and mean BMI z-score was 1.72 (sd 1.34) (girls 1.71 (sd 1.16); boys 1.72 (sd 1.11)). Serum leptin levels were significantly related to: sex (mean: girls 48.0 ng/ml, boys 34.4 ng/ml; P = 0.003); Tanner stage (mean: I-II 37.0 ng/ml, III-V 45.2 ng/ml; P = 0.035); systolic blood pressure (mean: normal 41.3 ng/ml, high 44.0 ng/ml; P = 0.009); BMI z-score (r 0.136; P = 0.010); C-peptide (r 0.17; P = 0.002); insulin (r 0.34; P < 0.001); homeostasis model assessment of insulin resistance (HOMA-IR) (r 0.25; P < 0.001) and aspartate aminotransferase (r - 0.12; P = 0.023). In the multivariate analysis (with leptin as the dependent variable and sex, Tanner stage, BMI z-score, systolic blood pressure, aspartate aminotransferase, C-peptide, insulin and HOMA-IR as independent variables), sex and BMI were determinant factors. The present study in overweight children and adolescents showed that being female and greater BMI were significantly and independently associated with increased serum leptin. In this large cohort other associations with leptin described in the literature can be discharged.
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PMID:Serum leptin levels in overweight children and adolescents. 1875 49

Fifty-one Jersey bull calves (5 +/- 1 d old) were assigned to 1 of 3 milk replacers to determine the effects of increasing doses of n-3 fatty acids from fish oil on the acute phase response after an endotoxin challenge. All calves were fed a 22.5% crude protein and 18% lipid milk replacer (Calva Products, Acampo, CA) supplemented with an additional 2% fatty acids. Treatments differed only in the supplemental lipid source and included a 3:1 mix of corn and canola oils, a 1:1 blend of fish oil (Omega Proteins, Houston, TX) and the 3:1 mix of corn and canola oils, and fish oil only. On d 23, each calf was injected subcutaneously with 4 microg/kg of body weight of Salmonella Typhimurium endotoxin. Clinical, hematological, and biochemical parameters were measured at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 15, 18, 24, and 72 h post endotoxin challenge. Endotoxin caused a dramatic rise in respiratory rate; feeding fish oil significantly attenuated the increase. Heart rate and rectal temperature were not affected by treatment. Feeding fish oil attenuated the change in serum iron concentration over time. Endotoxin caused severe hypoglycemia, reaching a nadir at 4 h. Calves supplemented with fish oil had reduced concentrations of serum glucose for 8 to 24 h. Furthermore, calves supplemented with fish oil alone had reduced serum insulin at 12, 28, and 24 h. In contrast, endotoxin caused an acute increase in blood urea nitrogen and nonesterified fatty acids; there were significant linear effects of fish oil on both blood urea nitrogen and nonesterified fatty acids. Serum triglycerides were elevated beginning at 12 h after the endotoxin challenge and returned to baseline values within 72 h. Fish oil suppressed the rise in triglycerides during this period, and the effect was linear with increasing fish oil. Serum concentrations of leptin decreased after the endotoxin challenge; however, the treatment did not influence the response. There was no treatment effect on serum aspartate aminotransferase or lactate dehydrogenase activity. Adding fish oil to milk replacer attenuated many aspects of the acute phase response, and the effect was linear in the range of 5 to 10% of the lipid replaced as fatty acids from fish oil. Adding fish oil might provide a better balance between a necessary versus an excessive acute phase response.
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PMID:Modifying the acute phase response of Jersey calves by supplementing milk replacer with omega-3 fatty acids from fish oil. 1876 7

We have currently studied the changes induced by administration of a fructose-rich diet (FRD) to normal rats in the mass and the endocrine function of abdominal (omental) adipose tissue (AAT). Rats were fed ad libitum a standard commercial chow and tap water, either alone (control diet, CD) or containing fructose (10%, w/vol) (FRD). Three weeks after treatment, circulating metabolic markers and leptin release from adipocytes of AAT were measured. Plasma free fatty acids (FFAs), leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were significantly higher in FRD than in CD rats. AAT mass was greater in FRD than in CD rats and their adipocytes were larger, they secreted more leptin and showed impaired insulin sensitivity. While leptin mRNA expression increased in AAT from FRD rats, gene expression of insulin receptor substrate, IRS1 and IRS2 was significantly reduced. Our study demonstrates that administration of a FRD significantly affects insulin sensitivity and several AAT endocrine/metabolic functions. These alterations could be part of a network of interacting abnormalities triggered by FRD-induced oxidative stress at the AAT level. In view of the impaired glucose tolerance observed in FRD rats, these alterations could play a key role in both the development of metabolic syndrome (MS) and beta-cell failure.
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PMID:Fructose-rich diet-induced abdominal adipose tissue endocrine dysfunction in normal male rats. 1916 36


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