The influence of obesity and different fat depots on adipose tissue gene expression and protein levels of cell adhesion molecules.

Increased circulating adhesion molecules in patients with obesity play an important role in the development of endothelial dysfunction/atherosclerosis. The aim of this study was to assess the contribution of various fat depots to the production of adhesion molecules in obesity. 12 women with first and second degree of obesity, 13 women with third degree of obesity and 14 lean age-matched women were included into study. Circulating levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were measured by Luminex kits. mRNA expression of ICAM-1, VCAM-1, E-selectin, monocyte chemoattractant protein-1 (MCP-1), and CD68 in subcutaneous (SAT) and visceral adipose tissue (VAT) was measured by RT-PCR; ICAM-1 and VCAM-1 protein levels by Luminex kits, normalized to protein content. Obesity increased ICAM-1 and VCAM-1 mRNA expression and protein levels and CD68 mRNA expression in VAT. Expression of E-selectin and MCP-1 did not significantly differ between groups. Expression of ICAM-1 and VCAM-1 positively correlated with expression of CD68 in both adipose depots. In VAT, ICAM-1 and VCAM-1 expression and protein levels positively correlated with BMI. Obesity was associated with increased adhesion molecules mRNA expression and protein levels in VAT, but not in SAT. Increased adhesion molecules production in visceral fat may provide a novel direct link between visceral adiposity and increased risk of cardiovascular complications.

The effect of pheochromocytoma treatment on subclinical inflammation and endocrine function of adipose tissue.

The aim of our study was to evaluate the influence of surgical removal of pheochromocytoma on the endocrine function of adipose tissue and subclinical inflammation as measured by circulating C-reactive protein (CRP) levels. Eighteen patients with newly diagnosed pheochromocytoma were included into study. Anthropometric measures, biochemical parameters, serum CRP, leptin, adiponectin and resistin levels were measured at the time of diagnosis and six months after surgical removal of pheochromocytoma. Surgical removal of pheochromocytoma significantly increased body weight, decreased both systolic and diastolic blood pressure, fasting blood glucose and glycated hemoglobin levels. Serum CRP levels were decreased by 50 % six months after surgical removal of pheochromocytoma (0.49+/-0.12 vs. 0.23+/-0.05 mg/l, p<0.05) despite a significant increase in body weight. Serum leptin, adiponectin and resistin levels were not affected by the surgery. We conclude that increased body weight in patients after surgical removal of pheochromocytoma is accompanied by an attenuation of subclinical inflammation probably due to catecholamine normalization. We failed to demonstrate an involvement of the changes in circulating leptin, adiponectin or resistin levels in this process.

[The influence of very-low-calorie diet on soluble adhesion molecules and their gene expression in adipose tissue of obese women]. / Vliv nízkokalorické diety na sérové koncentrace a expresi cytoadhezivních molekul v tukové tkáni u obézních zen.

BACKGROUND: Adhesion molecules (AM) are proteins expressed on the endothelial surface that play an important role in development of endothelial dysfunction. Higher concentrations of AM were found in patients with atherosclerosis, obesity or type 2 diabetes mellitus. The aim of our study was to measure serum concentrations and gene expression of ICAM-1 (intercellular adhesion molecule 1), VCAM-1 (vascular adhesion molecule 1) and E-selectin in subcutaneous adipose tissue samples obtained by needle biopsy from obese women and healthy controls and to evaluate the effect of 3-weeks very-low-calorie diet (VLCD) on these parameters. METHODS AND RESULTS: 20 obese women (BMI 46.2 +/- 9.7 kg/m2) and 13 lean control women (BMI 23.8 +/- 2.3 kg/m2) were included into the study. Gene expression of AM in subcutaneous adipose tissue was measured using RT-PCR, serum AM levels were measured by multiplex immunoanalysis. At the baseline, serum E-selectin concentrations were higher in obese women compared to controls (24.4 +/- 2.3 vs. 15 +/- 1,5 ng/ml, p < 0,05). 3 weeks of VLCD significantly decreased BMI and serum E-selectin levels. Baseline mRNA expression of E-selectin, ICAM-1 and VCAM-1 in subcutaneous adipose tissue was lower in obese relative to lean women (p < 0.05). Weight reduction increased ICAM-1 and VCAM-1 gene expression (p < 0.05). CONCLUSIONS: Our results suggest that the subcutaneous adipose tissue is not the major source of the studied soluble adhesion molecules in obese women and that the regulation of AM local gene expression in subcutaneous adipose tissue probably differs from its circulating levels.

Increased angiotensinogen production in epicardial adipose tissue during cardiac surgery: possible role in a postoperative insulin resistance.

Critical illness induces among other events production of proinflammatory cytokines that in turn interfere with insulin signaling cascade and induce insulin resistance on a postreceptor level. Recently, local renin-angiotensin system of adipose tissue has been suggested as a possible contributor to the development of insulin resistance in patients with obesity. The aim of our study was to determine local changes of the renin-angiotensin system of subcutaneous and epicardial adipose tissue during a major cardiac surgery, which may serve as a model of an acute stress potentially affecting endocrine function of adipose tissue. Ten patients undergoing elective cardiac surgery were included into the study. Blood samples and samples of subcutaneous and epicardial adipose tissue were collected at the beginning and at the end of the surgery. Blood glucose, serum insulin and adiponectin levels were measured and mRNA for angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1 receptor were determined in adipose tissue samples using RT PCR. Cardiac surgery significantly increased both insulin and blood glucose levels suggesting the development of insulin resistance, while serum adiponectin levels did not change. Expression of angiotensinogen mRNA significantly increased in epicardial adipose tissue at the end of surgery relative to baseline but remained unchanged in subcutaneous adipose tissue. Fat expression of angiotensin-converting enzyme and type 1 receptor for angiotensin II were not affected by surgery. Our study suggests that increased angiotensinogen production in epicardial adipose tissue may contribute to the development of postoperative insulin resistance.

Adiponectin and resistin gene polymorphisms in patients with anorexia nervosa and obesity and its influence on metabolic phenotype.

Genes for adiponectin and resistin are candidate genes of insulin resistance and type 2 diabetes mellitus. The aim of our study was to determine the frequency of single nucleotide polymorphisms (SNP) 45T>G and 276G>T of the adiponectin gene and 62G>A and -180C>G of the resistin gene in patients with obesity (OB), anorexia nervosa (AN) and in control healthy normal-weight women (NW) and to study the influence of particular genotypes on serum concentrations of these hormones and on insulin sensitivity. Serum adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), insulin, cholesterol, glycated hemoglobin (HbA1c) and blood glucose levels were measured in 77 patients with OB, 28 with AN and 38 NW. DNA analysis was carried out by polymerase chain reaction with restriction analysis of PCR product. The presence of SNP ADP+276 G>T allele was accompanied by higher cholesterol levels in AN patients, higher adiponectin concentrations in OB patients and lower HbA1c levels in NW. SNP of the resistin gene 62G>A was associated with lower HbA1c in NW and higher cholesterol concentrations in OB group. The carriers of the minor G allele in the position -180 of the resistin gene within AN group had significantly higher BMI relative to non-carriers. We conclude that polymorphisms in adiponectin and resistin genes can contribute to metabolic phenotype of patients with obesity and anorexia nervosa.

[Pilot study to evaluate blood glucose control by a model predictive control algorithm with variable sampling rate vs. routine glucose management protocol in peri- and postoperative period in cardiac surgery patients]. / Pilotní studie pro srovnání pocítacového algoritmu s variabilním intervalem merení glykémie a standardního protokolu pro intenzivní inzulínovou terapii v peri- a pooperacním období u kardiochirurgických pacientu.

BACKGROUND: Increased blood glucose levels are frequently observed in critically ill patients. Recent studies have shown that the normalization of glycemia by intensive insulin therapy decreases mortality, length of the hospitalization and number of complications. METHODS AND RESULTS: The aim of this pilot study was to compare blood glucose control by an automated model predictive control algorithm with variable sampling rate (eMPC) with routine glucose management protocol (RP) in peri- and postoperative period in cardiac surgery patients. 20 patients were included into this study (14 men and 6 women, mean age 68 +/- 10 let, BMI 28.3 +/- 5.0 kg/m2). 10 patients were randomized for treatment using eMPC algorithm and 10 patients for routine protocol. All patients underwent elective cardiac surgery and were treated with continuous insulin infusion to maintain glycemia in target range 4.4-6.1 mmol/l. The study duration was 24 hours. Mean blood glucose was significantly lower in eMPC vs. RP group (5.80 +/- 0.45 vs. 7.23 +/- 0.84 mmol/l, p < 0.05). Percentage of time in target range was significantly higher in eMPC vs. RP group (67.6 +/- 8.7% vs. 27.6 +/- 15.8%, p < 0.05). Percentage of time above the target range was higher in RP vs. eMPC group. Average insulin infusion rate was higher in eMPC vs. RP group (4.18 +/- 1.19 vs. 3.24 +/- 1.43 IU/hour, p < 0.05). Average sampling interval was significantly shorter in eMPC vs. RP group (1.51 +/- 0.24 vs. 2.03 +/- 0.16 hour, p < 0.05). No severe hypoglycaemia in either group occurred during the study. CONCLUSIONS: The results of our pilot study suggest that eMPC algorithm is more effective in maintaining euglycemia in peri- and post-operative period in patients after cardiac surgery and comparably safe as compared to RP.

Effect of PPAR-gamma agonist treatment on markers of endothelial dysfunction in patients with type 2 diabetes mellitus.

Thiazolidinediones are insulin-sensitizing drugs acting through peroxisome proliferator-activated receptor (PPAR)-gamma. The aim of our study was to evaluate the effect of 5-month treatment with PPAR-gamma agonist--rosiglitazone (4 mg/day), on the circulating markers of endothelial dysfunction and to evaluate the role of changes in endocrine function of adipose tissue in this process. Biochemical and metabolic parameters, circulating adiponectin, resistin, ICAM-1, VCAM-1, E-selectin, P-selectin, PAI-1, myeloperoxidase (MPO), and matrix metalloproteinase-9 (MMP-9) concentrations were assessed in 10 women with type 2 DM before and after rosiglitazone treatment and in a control group of healthy women. At baseline, diabetic group had significantly higher serum concentrations of glucose, glycated hemoglobin, V-CAM and PAI-1 compared to control group. Adiponectin levels tended to be lower in diabetic group, while resistin concentrations did not differ from control group. Rosiglitazone treatment improved diabetes compensation, significantly reduced VCAM-1, PAI-1 and E-selectin concentrations and increased adiponectin levels, while it did not affect serum resistin concentrations. Adiponectin concentrations at baseline were inversely related to E-selectin and MPO levels, this correlation disappeared after rosiglitazone treatment. We conclude that 5-month rosiglitazone treatment significantly reduced several markers of endothelial dysfunction. This effect could be at least in part attributable to marked increase of circulating adiponectin levels.

Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes.

PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle.

[The treatment of hyperglycaemia in critically ill patients: comparison of standard protocol and computer algorithm]. / Lécba hyperglykemie u kriticky nemocných pacientu: srovnání standardního protokolu a pocítacového algoritmu.

INTRODUCTION: Hyperglycemia is commonly observed in patients hospitalized on intensive care units. It is has been demonstrated that normalization of blood glucose level using intensive insulin therapy significantly improves prognosis of these patients. The aim of our study was comparison of standard protocol of intensive insulin therapy used on cardiac surgery ICU in General University Hospital in Prague and computer algorithm MPC (Model Predictive Control). PATIENTS AND METHODS: 20 patients with glycaemia higher than 6.7 mmol/l at the time of admission to ICU were included into the study, 10 subjects were randomized for standard treatment, 10 for treatment with MPC algorithm. Glycaemia was measured hourly during 48 hours, insulin infusion was rate was adjusted hourly in MPC algorithm or in 1-2 hours in standard protocol group. RESULTS: Blood glucose levels were in the target range significantly longer in MPC relative to standard protocol group (26.3 +/- 2.1 hrs vs 20.3 +/- 2.5 hrs). Mean blood glucose was also lower using MPC algorithm (6.47 +/- 0.11 vs 6.72 +/- 0.23 mmol/l). On the contrary the target range was established faster using standard protocol (8.9 +/- 1.2 vs 10.3 +/- 0.9 hrs), duration of hyperglycaemia was the same in both groups (7.3 +/- 1.9 in standard protocol vs 7.3 +/- 1.3 hrs in MPC algorithm). Average 48-hours insulin dose was higher in MPC than standard protocol group (230.2 +/- 38.8 vs 199.1 +/- 27.8 IU/48 hrs). 2 hypoglycaemic episodes occured in 2 patients in standard protocol group. CONCLUSIONS: Our results show that the use of MPC algorithm result in more effective blood glucose control in critically ill patients than standard protocol.

[Polymorphisms of adiponectin and resistin genes in patients with obesity and anorexia nervosa]. / Polymorfismy genu pro adiponectin a rezistin u pacientek s mentální anorexií a obezitou--pilotní studie.

BACKGROUND: Adiponectin and resistin are hormones that may represent a link between obesity and insulin resistance. Genes for these hormones are new candidate genes of insulin resistance and type 2 diabetes mellitus. The aim of our study was to determine the frequency of single nucleotide polymorphisms 45T > G and 276T > G of adiponectin gene and 62G > A and -180C > G of resistin gene in patients with obesity, anorexia nervosa and in lean women and to study the influence of particular genotypes on serum concentrations of these hormones. METHODS AND RESULTS: Serum adiponectin, resistin, TNF-alfa and insulin levels were measured in 51 patients with obesity, 17 with anorexia nervosa and 17 lean women. DNA analysis was carried out by means of polymerase chain reaction (PCR) with restriction analysis of PCR product (RFLP). Adiponectin levels were lowest in obese women and highest in anorexia nervosa patients. Resistin concentrations were lowest in anorexia nervosa and highest in obese patients. Genotype analysis within respective groups showed no differences in assessed parameters when comparing different adiponectin and resistin polymorphisms. The only difference detected was significantly higher BMI in G/G genotype relative to T allele carries in 276 position of ADP gene in control group (23.48 +/- 0.85 vs. 19,7 +/- 0.95, p < 0.05). In anorexia nervosa patients, frequency of G allele in RETN -180 polymorphism was significantly higher relative to control group (p < 0.05). CONCLUSIONS: Polymorphisms 45T > G a 276T > G of ADP gene and 62G>A and -180C > G RETN gene did not influence serum ADP and RETN concentrations. BMI was influenced by T allele presence in 276 position of ADP gene in control group only. Anorexia nervosa patients had higher frequency of G allele of RETN -180 polymorphism compared to healthy women.

Tobacco use amongst high school students in the Czech Republic.

OBJECTIVE: We were interested in the prevalence of smoking amongst teen-age students, its possible causes, and their understanding of its associated health risks. METHODS: We constructed a questionnaire that was responded to by a total of 419 students from 5 high schools in Prague, Czech Republic. Students were classified as non-smokers, mild (1-10 cigarettes daily), moderate (11-20 cigarettes daily), and severe smokers (>20 cigarettes daily). The survey also contained questions about passive smoking, motivation for smoking, the understanding of its associated health risks, alcohol consumption, and drugs. RESULTS: We found that amongst 16-20 years old high school students there are 37.5% smokers (38.0% men, and 37.0% women). The majority are mild smokers (82.3%), 15.8% moderate smokers and 1.9% heavy smokers. 29.0% of non-smokers reported passive smoking; i.e. that 65.7% of students are exposed to harmful effect of tobacco smoke. The average onset of smoking is at 14 years of age. The youngest smoker started smoking at the age of 5 years. Parents of 52.0% of students smoke (69.4% of smokers and 41.6% of non-smokers). Most of students know about the risk of lung cancer and cardiovascular diseases (86-99%). CONCLUSIONS: The prevalence of active and passive smoking among high school students is high. Parents smoking is significantly more frequent in teen-age smokers than in non-smokers. We consider the "teen-age" population together with their parents to be the key target for a successful antismoking campaign.