Denisa Haluzikova

Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity.

Objective  Fibroblast growth factor‐21 (FGF21) is a novel endocrine and paracrine regulator of metabolic homeostasis. The aim of our study was to measure its serum concentrations in patients with obesity, obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C), and to assess the changes of its circulating levels and mRNA expression after dietary and pharmacological interventions.

Plasma Concentrations of Fibroblast Growth Factors 19 and 21 in Patients with Anorexia Nervosa

CONTEXT Fibroblast growth factor 19 (FGF19) and FGF21 are novel metabolic regulators that improve insulin sensitivity and decrease adiposity in mice. However, little is known about the nutritional regulation of these factors in humans. OBJECTIVE The objective of this study was to measure plasma FGF19 and FGF21 levels in patients with anorexia nervosa (AN) and to explore its relationship with anthropometric and endocrine parameters. DESIGN This was a single-center cross-sectional study. SETTING The study was performed in a university hospital. PATIENTS Seventeen untreated women with a restrictive type of AN and 17 healthy women (control group) were included. MAIN OUTCOME MEASURES Fasting plasma FGF19 and FGF21, serum insulin, leptin, soluble leptin receptor, adiponectin, resistin, and C-reactive protein were the main outcome measures. RESULTS Plasma FGF19 levels did not significantly differ between the groups studied, whereas plasma FGF21 levels were significantly reduced in AN relative to the control group. Plasma FGF21 positively correlated with body mass index and serum leptin and insulin and was inversely related to serum adiponectin in both groups. In contrast, plasma FGF19 was not related to any of parameters studied. Partial realimentation significantly reduced plasma FGF21 levels in AN. CONCLUSION Circulating levels of FGF21 but not FGF19 are strongly related to body weight and serum levels of leptin, adiponectin, and insulin in both anorectic and normal-weight women. We suggest that reduced plasma FGF21 levels could be involved in the pathophysiology of AN or in a complex adaptive response to this disease.

The endocrine profile of subcutaneous and visceral adipose tissue of obese patients

The aim of the present study was to evaluate the expression profile of genes potentially related to metabolic complications of obesity in the whole adipose tissue and isolated adipocytes from subcutaneous (SAT) and visceral adipose tissue (VAT) from 12 non-diabetic obese women and 12 lean women. Real-time polymerase chain reaction was used for expression analysis of 41 genes of interest and two housekeeping genes. We found increased expression of specific proinflammatory and adipogenic genes and reduced expression of specific lipogenic and insulin signaling pathway genes in obese relative to lean women with no preferable localization in SAT or VAT depot. The gene expression significantly differed between adipocytes and adipose tissue but both contributed to the proinflammatory profile in obesity. We conclude that both SAT and VAT exhibit alterations in the expression of specific genes possibly contributing to proinflammatory and insulin resistance state and consequently to metabolic complications of obesity.

Increased serum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus: the influence of very low calorie diet

OBJECTIVE Macrophage inhibitory cytokine-1 (MIC-1) is a novel regulator of energy homeostasis. We explored whether alterations in MIC-1 levels contribute to metabolic disturbances in patients with obesity and/or obesity and type 2 diabetes mellitus (T2DM). DESIGN We measured serum MIC-1 levels and its mRNA expression in subcutaneous and visceral adipose tissue of 17 obese nondiabetic women, 14 obese women with T2DM and 23 healthy lean women. We also explored the relationship of MIC-1 with anthropometric and biochemical parameters and studied the influence of 2-week very low calorie diet (VLCD) on serum MIC-1 levels. METHODS Serum MIC-1 levels were measured by ELISA and its mRNA expression was determined by RT-PCR. RESULTS Both obese and T2DM group had significantly elevated serum MIC-1 levels relative to controls. T2DM group had significantly higher serum MIC-1 levels relative to obese group. Serum MIC-1 positively correlated with body weight, body fat, and serum levels of triglycerides, glucose, HbAlc, and C-reactive protein and it was inversely related to serum high-density lipoprotein cholesterol. Fat mRNA MIC-1 expression did not significantly differ between lean and obese women but it was significantly higher in subcutaneous than in visceral fat in both groups. VLCD significantly increased serum MIC-1 levels in obese but not T2DM group. CONCLUSION Elevated MIC-1 levels in patients with obesity are further increased by the presence of T2DM. We suggest that in contrast to patients with cancer cachexia, increased MIC-1 levels in obese patients and diabetic patients do not induce weight loss.

Laparoscopic sleeve gastrectomy differentially affects serum concentrations of FGF-19 and FGF-21 in morbidly obese subjects

Fibroblast growth factor (FGF)‐19 and FGF‐21 are novel metabolic regulators that improve insulin resistance and obesity in rodents. The aim of the study was to assess the effects of laparoscopic sleeve gastrectomy (LSG) on serum concentrations of FGF‐19 and FGF‐21 along with circulating bile acids and other relevant hormonal and biochemical parameters.

The Effect of Very-Low-Calorie Diet on mRNA Expression of Inflammation-Related Genes in Subcutaneous Adipose Tissue and Peripheral Monocytes of Obese Patients with Type 2 Diabetes Mellitus

CONTEXT Low-grade inflammation links obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases. OBJECTIVE To explore the expression profile of genes involved in inflammatory pathways in adipose tissue and peripheral monocytes (PM) of obese patients with and without T2DM at baseline and after dietary intervention. DESIGN Two-week intervention study with very-low-calorie diet (VLCD). SETTING University hospital. PATIENTS Twelve obese females with T2DM, 8 obese nondiabetic females (OB) and 15 healthy age-matched females. INTERVENTION Two weeks of VLCD (2500 kJ/d). MAIN OUTCOME MEASURES Metabolic parameters, circulating cytokines, hormones, and mRNA expression of 39 genes in sc adipose tissue (SCAT) and PM. RESULTS Both T2DM and OB group had significantly increased serum concentrations of circulating proinflammatory factors (C-reactive protein, TNFα, IL-6, IL-8), mRNA expression of macrophage antigen CD68 and proinflammatory chemokines (CCL-2, -3, -7, -8, -17, -22) in SCAT and complementary chemokine receptors (CCR-1, -2, -3, -5) and other proinflammatory receptors (toll-like receptor 2 and 4, TNF receptor superfamily 1A and 1B, IL-6R) in PM, with OB group showing less pronounced chemoattracting and proinflammatory profile compared to T2DM group. In T2DM patients VLCD decreased body weight, improved metabolic profile, and decreased mRNA expression of up-regulated CCRs in PM and chemokines [CCL 8, chemokine (C-X-C motif) ligand 10] in SCAT. VLCD markedly increased mRNA expression of T-lymphocyte attracting chemokine CCL-17 in SCAT. CONCLUSION Obese patients with and without T2DM have increased mRNA expression of chemotactic and proinflammatory factors in SCAT and expression of corresponding receptors in PM. Two weeks of VLCD significantly improved this profile in T2DM patients.

Increased production of proinflammatory cytokines in adipose tissue of patients with end-stage renal disease.

OBJECTIVE The number of patients with end-stage renal disease (ESRD) is rising and these patients are at higher risk of cardiovascular disease. We studied the role of hormonal production of adipose tissue in the development of chronic inflammation in patients with ESRD before kidney transplantation. METHODS Fifteen women with ESRD and 17 healthy women (control) underwent single blood drawing and visceral and subcutaneous adipose tissue sampling during surgery (kidney transplantation in the ESRD group or cholecystectomy in the control group). Serum concentrations of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, resistin, monocyte chemoattractant protein-1 were measured. Messenger RNA expression of the same hormones, adiponectin receptors 1 and 2 and immunocompetent cell marker CD68 in subcutaneous and visceral samples were measured using real-time polymerase chain reaction. Adipose tissue was examined immunohistochemically for CD68-positive cells. RESULTS Serum concentrations of C-reactive protein, adiponectin, resistin, interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 were significantly higher in the ESRD versus control group. Subcutaneous and visceral mRNA expressions of tumor necrosis factor-alpha and CD68 were significantly increased in the ESRD versus control group. Adiponectin receptor-1 and monocyte chemoattractant protein-1 mRNA expressions were significantly higher in visceral but not in subcutaneous adipose tissue of the ESRD group. Messenger RNA expressions of resistin, leptin, adiponectin, interleukin-6, and adiponectin receptor-2 in both fat depots did not significantly differ between groups. Increased infiltration of subcutaneous and visceral adipose tissue with CD68-positive immunocompetent cells was found in the ESRD group by histologic examination. CONCLUSION Subcutaneous and visceral adipose tissues in ESRD express higher amounts of proinflammatory cytokines and may play a role in the development of systemic inflammation.

Changes of endocrine function of adipose tissue in anorexia nervosa: comparison of circulating levels versus subcutaneous mRNA expression.

Objective  To study the influence of chronic malnutrition in patients with anorexia nervosa on endocrine function of adipose tissue on both circulating and subcutaneous fat mRNA expression level.

Soluble leptin receptor levels in patients with anorexia nervosa

Objective: To examine whether changes of serum soluble leptin receptor levels (S-LEPR) can modify leptin half-life and its tissue effects. The aim of our study was to measure S-LEPR levels in patients with anorexia nervosa (AN) before and 6 weeks after partial refeeding. Methods: Anthropometric variables, serum leptin, S-LEPR, insulin, cortisol and TNF-alpha were measured in 15 AN patients before and after partial refeeding and 15 healthy control women. Results: S-LEPR levels in AN patients were significantly higher than in healthy subjects (26.8±8.1 vs. 16.36±2.6 U/mL, p<0.01) and were not affected by partial refeeding (26.8±8.1 vs. 24.2±6.1 U/mL). In contrast, body mass index (BMI), body fat content, and serum leptin levels in AN patients increased significantly after partial refeeding. Except for the inverse relationship of S-LEPR levels to BMI and body fat content no clear relationship of this parameter to serum leptin, cortisol, insulin or TNF-alpha was found. Conclusion: S-LEPR levels are significantly increased in AN patients and this increase is unaffected by partial refeeding. The possibility of etiological role of increased S-LEPR levels in AN patients by affecting leptin central and/or peripherial effects should be further elucidated.

Lower serum leptin concentrations in rugby players in comparison with healthy non-sporting subjects – relationships to anthropometric and biochemical parameters

Abstract Leptin is a protein hormone synthesized by adipocytes. Its serum concentrations reflect the total body fat content. Serum leptin concentrations are significantly higher in obese than in lean people and in women than in men. However little information about the influence of physical activity on serum leptin concentrations is available. We have compared the body weight, the body mass index (BMI), the body fat content (measured by caliper as skinfold thickness) and the serum concentrations of leptin, triglycerides, total, high density and low density lipoprotein (LDL) cholesterol in 14 top rugby players and 10 healthy controls. We found that serum leptin, total and LDL cholesterol concentrations were significantly lower in the rugby players group than in the control subjects. The body weight and BMI were significantly higher in the rugby players, while the body fat content was only slightly (non-significantly) higher in the control group. The serum leptin concentrations in both groups positively correlated with the BMI and body fat content and also with LDL concentrations in the control group. The serum leptin concentrations in the rugby players were lower than in the non-sporting subjects despite a similar body fat content in both groups. We would therefore suggest the possibility that regular hard physical training decreases serum leptin concentrations not only by the decrease of total body fat content, but also by a separate mechanism, which is not directly dependent on the changes in the amount of body adipose tissue.