Marketa Bartlova

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.

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.

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.

Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus

The purpose of this study was to assess the expression profile of genes with potential role in the development of insulin resistance (adipokines, cytokines/chemokines, estrogen receptors) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placenta of pregnant women with gestational diabetes mellitus (GDM) and age-matched women with physiological pregnancy at the time of Caesarean section. qRT-PCR was used for expression analysis of the studied genes. Leptin gene expression in VAT of GDM group was significantly higher relative to control group. Gene expressions of interleukin-6 and interleukin-8 were significantly increased, whereas the expressions of genes for estrogen receptors alpha and beta were significantly reduced in SAT of GDM group relative to controls, respectively. We found no significant differences in the expression of any genes of interest (LEP, RETN, ADIPOR1, ADIPOR2, TNF-alpha, CD68, IL-6, IL-8, ER alpha, ER beta) in placentas of women with GDM relative to controls. We conclude that increased expression of leptin in visceral adipose depot together with increased expressions of proinflammatory cytokines and reduced expressions of estrogen receptors in subcutaneous fat may play a role in the etiopathogenesis of GDM.

The influence of deep hypothermia on inflammatory status, tissue hypoxia and endocrine function of adipose tissue during cardiac surgery

Changes in endocrine function of adipose tissue during surgery, such as excessive production of proinflammatory cytokines, can significantly alter metabolic response to surgery and worsen its outcomes and prognosis of patients. Therapeutic hypothermia has been used to prevent damage connected with perioperative ischemia and hypoperfusion. The aim of our study was to explore the influence of deep hypothermia on systemic and local inflammation, adipose tissue hypoxia and adipocytokine production. We compared serum concentrations of proinflammatory markers (CRP, IL-6, IL-8, sIL-2R, sTNFRI, PCT) and mRNA expression of selected genes involved in inflammatory reactions (IL-6, TNF-α, MCP-1, MIF) and adaptation to hypoxia and oxidative stress (HIF1-α, MT3, GLUT1, IRS1, GPX1, BCL-2) in subcutaneous and visceral adipose tissue and in isolated adipocytes of patients undergoing cardiosurgical operation with hypothermic period. Deep hypothermia significantly delayed the onset of surgery-related systemic inflammatory response. The relative gene expression of the studied genes was not altered during the hypothermic period, but was significantly changed in six out of ten studied genes (IL-6, MCP-1, TNF-α, HIF1-α, GLUT1, GPX1) at the end of surgery. Our results show that deep hypothermia suppresses the development of systemic inflammatory response, delays the onset of local adipose tissue inflammation and thus may protect against excessive expression of proinflammatory and hypoxia-related factors in patients undergoing elective cardiac surgery procedure.