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Aldoketoreductase 1C3 (AKR1C3) is a functional prostaglandin F synthase and a negative modulator of the availability of ligands for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ). AKR1C3 expression is known to be associated with adiposity, one of the components of the metabolic syndrome. The aim of this study was to characterize the expression of AKR1C3 in the adipose tissue and adipocytes and to investigate its potential role in the metabolic syndrome. Using microarray analysis and realtime PCR, we studied the expression of AKR1C3 in adipose tissue samples from obese subjects with or without metabolic complications, during very low calorie diet-induced weight loss, and its expression in isolated human adipocytes of different sizes. The adipose tissue AKR1C3 expression levels were marginally lower in obese subjects with the metabolic syndrome compared with the levels in healthy obese subjects when analyzed using microarray (p = 0.078) and realtime PCR (p < 0.05), suggesting a secondary or compensatory effect. The adipose tissue mRNA levels of AKR1C3 were reduced during and after dietinduced weight-loss compared to the levels before the start of the diet (p < 0.001 at all time-points). The gene expression of AKR1C3 correlated with both adipose tissue mRNA levels and serum levels of leptin before the start of the diet (p < 0.05 and p < 0.01, respectively). Furthermore, large adipocytes displayed a higher expression of AKR1C3 than small adipocytes (1.5-fold, p < 0.01). In conclusion, adipose tissue AKR1C3 expression may be affected by metabolic disease, and its levels are significantly reduced in response to dietinduced weight loss and correlate with leptin levels.
Leptin, 16- kDa protein produced and secreted from white adipocytes is known to regulate food intake and energy expenditure. Leptin receptors have been detected in the pancreas and it has been shown that systemic application of this protein diminished postprandial pancreatic secretion. Leptin is also produced in the stomach and released into the gastrointestinal lumen but the implication of luminal leptin in the regulation of pancreatic enzyme secretion has not been elucidated. The aim of our study was to evaluate the effects of intraduodenal (i.d.) leptin administration on pancreatic enzyme secretion and to assess the involvent of afferent nerves and CCK in above effects. The secretory studies were carried out on anaesthetized Wistar rats with acute pancreatic fistulae. Leptin was administered to the animals at doses of 0.1 1.0 or 10.0 µg/kg i.d. Tarazepide (2.5 mg/kg i.d.), a CCK1 receptor antagonist, was given to the rats prior to the application of leptin. Rats with capsaicin deactivated sensory nerves were used in part of the study. Samples of pancreatic juice were taken at 15 min intervals to measure the volume flow and protein and amylase concentrations. CCK plasma level was measured by radioimmunoassay (RIA) following administration of leptin to the rats. Intraduodenal administration of leptin (1.0 or 10.0 µg/kg) to the fasted rats significantly and dose-dependently increased pancreatic protein and amylase outputs. Pancreatic secretory responses to leptin were totally abolished by prior capsaicin deactivation of sensory nerves or by pretreatment of the rats with tarazepide. Under basal conditions plasma CCK level averaged about 15.46 ± 1,4 pg/ml. Exogenous leptin, given i.d. at doses of 0.1 1.0 or 10.0 µg/kg i.d. to the rats with intact or capsaicin-deactivated sensory nerves resulted in dose-dependent rise of plasma CCK level, reaching the highest value at the dose of 10.0 µg/kg i.d. We conclude that leptin given i.d. stimulates pancreatic enzyme secretion and this effect could be related to the stimulation of CCK release and activation of duodeno-pancreatic reflexes.
Leptin is an adipocyte-derived hormone regulating energy homeostasis and body weight. Leptin also plays a role in hematopoesis, cell cycle regulation, and in oncogenesis. The leptin receptor is a single transmembrane protein belonging to the superfamily of cytokine receptors, structurally related to the hemopoietin receptor family. The aim of the study was to evaluate bone marrow and peripheral blood leptin level and frequency of distribution of leptin receptor gene polymorphism Gln223Arg in children with acute leukemia. The examined group included 92 children with acute leukemia (83 ALL and 9 AML) and 39 non-leukemic control children. Leptin level was measured by ELISA method at the day of leukemia diagnosis. Genomic DNA was isolated with the use of a column method and the genotyping of DNA sequence variation was carried out by the restriction enzyme analysis of PCR – amplified DNA. The samples were then electrophoresed on 2.5% agarose gel. Leptin level in leukemic children was lower than in healthy children. Bone marrow leptin level was significantly lower than that in the blood in leukemic children with ALL-T and AML. An analysis of frequency distribution of the Gln233Arg polymorphism in the leptin receptor gene in leukemic children showed lack of differences between the patients and controls. There was no difference in the genotype frequencies between the leukemic AML and ALL groups either. The results indicate a possible relation between the leptin level and leukemia development in children. The effectory effect of the hormone seems not related to Gln223Arg polymorphism of its receptor.
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Adipocytokines - novel link between inflammation and vascular funktion?

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Obesity and obesity related diseases are a major public health problem. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine and immune functions. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like TNF-alpha, IL-6, MCP-1 (CCL-2), IL-1. All of those molecules may act on immune cells leading to local and generalized inflammation and may also affect vascular (endothelial) function by modulating vascular nitric oxide and superoxide release and mediating obesity related vascular disorders (including hypertension, diabetes, atherosclerosis, and insulin resistance) but also cancer or non-alcoholic fatty liver diseases. Present review, in a concise form, focuses on the effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels. Macrophages and T cells are populating adipose tissue which develops into almost an organized immune organ. Activated T cells further migrate to blood vessels, kidney, brain and other organs surrounded by infiltrated fat leading to their damage, thus providing a link between metabolic syndrome, inflammation and cardiovascular and other associated disorders. Ceretain treatments may lead to significant changes in adipocytokine levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as well as androgens lead to decrease of plasma leptin levels. Moreover future treatments of metabolic system associated disorders should focus on the regulation of adipocytokines and their modes of action.
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