M Haluzík

Charles University in Prague, Praha, Praha, Czech Republic

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Publications (210)491.15 Total impact

  • Milos Mraz, Martin Haluzik
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    ABSTRACT: Adipose tissue lies at the crossroad of nutrition, metabolism and immunity and adipose tissue inflammation was proposed as a central mechanism connecting obesity with its metabolic and vascular complications. Resident immune cells constitute the second largest adipose tissue cellular component after adipocytes and as such play important roles in maintaining adipose tissue homeostasis. Obesity induced changes in their number and activity result in activation of local and later systemic inflammatory response marking the transition from simple adiposity to diseases like type 2 diabetes mellitus, arterial hypertension and ischemic heart disease. This review will focus on the various subsets of immune cells in adipose tissue and their role in the development of adipose tissue inflammation and obesity-induced insulin resistance.
    The Journal of endocrinology. 07/2014;
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    ABSTRACT: The only peripherally released orexigenic hormone, ghrelin, plays a key role in food intake and body weight regulation. Antagonizing the ghrelin receptor, GHS-R1a, represents a promising approach for anti-obesity therapy. In our study, two novel GHS-R1a antagonists JMV4208 and JMV3002, which are trisubstituted 1,2,4-triazoles, decreased food intake in fasted lean mice in a dose-dependent manner, with ED50 values of 5.25 and 2.05 mg/kg, respectively. Both compounds were stable in mouse blood, with half-lives of 90 min (JMV4208) and 60 min (JMV3002), and disappeared from the blood 8 hours after administration. Fourteen days of treatment with the ghrelin antagonists (20 mg/kg twice a day) decreased food intake, body weight and adipose tissue mass in mice with diet-induced obesity (DIO). These results are likely attributable to an impact on food intake reduction and an attenuated expression ot the lipogenesis-promoting enzymes (acetyl-CoA carboxylase 1 in subcutaneous fat and fatty acid synthase in subcutaneous and intraperitoneal fat). The decrease in fat mass negatively impacted circulating leptin levels. These data suggest that JMV4208 and JMV3002 could be useful therapeutic agents for the treatment of obesity.
    Molecular and Cellular Endocrinology 06/2014; · 4.04 Impact Factor
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    ABSTRACT: The aim of our study was to explore the effects of regular aerobic exercise on anthropometric, biochemical and hormonal parameters and mRNA expression of selected factors involved in metabolic regulations in subcutaneous adipose tissue of patients with obesity. Fifteen obese women with arterial hypertension underwent a three-month exercise program consisting of 30 min of aerobic exercise 3 times a week. Fifteen healthy lean women with no intervention served as a control group. Obese group underwent anthropometric measurements, blood sampling, subcutaneous adipose tissue (SCAT) biopsy and 24-h blood pressure monitoring at baseline and after three months of exercise, while control group was examined only once. At baseline, obese group had increased SCAT expression of proinflammatory cytokines and adipokines relative to control group. Three months of regular exercise improved anthropometric parameters, decreased CRP, blood glucose and HOMA-IR, while having no significant effect on lipid profile and blood pressure. Gene expressions in SCAT were not affected by physical activity with the exception of increased aquaporin-3 mRNA expression. We conclude that three months of regular exercise decrease systemic subclinical inflammation with only minor influence on the blood pressure and the endocrine function of subcutaneous fat.
    Physiological research / Academia Scientiarum Bohemoslovaca 06/2014; 63(Supplementum 2):S299-S308. · 1.53 Impact Factor
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    ABSTRACT: Patients with obesity and type 2 diabetes often display high levels of the anti-diabetic factor fibroblast growth factor-21 (FGF21), suggesting that the overproduction of FGF21 may result from increased adiposity in an attempt by white adipose tissue (WAT) to counteract insulin resistance. However, the production of FGF21 diabetes in the absence of WAT has not been examined. In this study, we investigated the effects of lipodystrophy in A-ZIP F-1 mice on FGF21 production in relation to diabetes. A-ZIP F-1 mice displayed high FGF21 plasma levels resulting from enhanced FGF21 mRNA expression in the liver. Concomitant enhancement of FGF21 receptor (FGFR1) and glucose transporter 1 (GLUT-1) mRNA expression was observed in the muscles of A-ZIP F-1 mice. Furthermore, the activation of hypothalamic NPY and AgRP mRNA expression positively correlated with plasma levels of FGF21 but not active ghrelin. Our study demonstrates that an increased FGF21 plasma level in lipodystrophic A-ZIP F-1 mice results mainly from up-regulated liver production but does not suffice to overcome the lipodystrophy-induced severe type 2-diabetes and insulin resistance in the liver linked to the augmented liver fat deposition.
    Physiological research / Academia Scientiarum Bohemoslovaca 06/2014; · 1.53 Impact Factor
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    ABSTRACT: During the last 2 decades, the treatment of hyperglycemia in critically ill patients has become one of the most discussed topics in the intensive medicine field. The initial data suggesting significant benefit of normalization of blood glucose levels in critically ill patients using intensive intravenous insulin therapy have been challenged or even neglected by some later studies. At the moment, the need for glucose control in critically ill patients is generally accepted yet the target glucose values are still the subject of ongoing debates. In this review, we summarize the current data on the benefits and risks of tight glucose control in critically ill patients focusing on the novel technological approaches including continuous glucose monitoring and its combination with computer-based algorithms that might help to overcome some of the hurdles of tight glucose control. Since increased risk of hypoglycemia appears to be the major obstacle of tight glucose control, we try to put forward novel approaches that may help to achieve optimal glucose control with low risk of hypoglycemia. If such approaches can be implemented in real-world practice the entire concept of tight glucose control may need to be revisited.
    Journal of diabetes science and technology 05/2014;
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    ABSTRACT: Laparoscopic sleeve gastrectomy (LSG) is a bariatric procedure with very good long-term weight-reducing and metabolic effects. Here we report 6 years' experience with LSG performed in morbidly obese patients by one surgical team focusing on the impact of the degree of sleeve restriction and safety of the procedure without over-sewing the staple line. From 2006 to 2012, 207 morbid obese patients with average age of 43.4 years and average body mass index 44.9 kg/m(2) underwent LSG without over-sewing the staple line. The complete 5- and 3-year follow-up is recorded in 59 and 117 patients with prospective data collection at 3, 6, 9, 12, 18, 24, 36, 42 and 60 months after LSG. Group 1 patients operated in 2006-2008 had smaller sleeve restriction. Group 2 patients operated in 2009-2012 had major sleeve restriction. All procedures were performed without over-sewing of the staple line. The average %EBMIL (excess body mass index loss) in group 1 patients with minor sleeve restriction reached 54.1% and average %EWL (excess weight loss) was 50.8% while in group 2 with major sleeve restriction the average %EBMIL reached 69.7% and average %EWL was 66.8%. Final weight reduction was significantly higher in group 2 patients compared to group 1 patients with smaller sleeve restriction. Out of 49 patients with preoperatively diagnosed T2DM (type 2 diabetes mellitus) was completely resolved in 70.8%. Pre-operatively diagnosed hypertension normalized in 64.2%, improved in 23.2%, and remained unchanged in 12.6% of patients. Carefully performed LSG without over-sewing the staple line is feasible and safe. A better weight-reducing effect was present in patients with major sleeve restriction.
    Videosurgery and Other Miniinvasive Techniques / Wideochirurgia i Inne Techniki Malo Inwazyjne 03/2014; 9(1):46-52. · 0.76 Impact Factor
  • Martin Haluzik, Denisa Haluziková
    Expert Review of Endocrinology &amp Metabolism 01/2014; 6(1).
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    ABSTRACT: Omentin is a novel adipokine with insulin-sensitizing effects expressed predominantly in visceral fat. We investigated serum omentin levels and its mRNA expression in subcutaneous adipose tissue (SCAT) of 11 women with type 2 diabetes mellitus (T2DM), 37 obese non-diabetic women (OB) and 26 healthy lean women (C) before and after various weight loss interventions: 2-week very-low-calorie diet (VLCD), 3-month regular exercise and laparoscopic sleeve gastrectomy (LSG). At baseline, both T2DM and OB groups had decreased serum omentin concentrations compared with C group while omentin mRNA expression in SCAT did not significantly differ among the groups. Neither VLCD nor exercise significantly affected serum omentin concentrations and its mRNA expression in SCAT of OB or T2DM group. LSG significantly increased serum omentin levels in OB group. In contrast, omentin mRNA expression in SCAT was significantly reduced after LSG. Baseline fasting serum omentin levels in a combined group of the studied subjects (C, OB, T2DM) negatively correlated with BMI, CRP, insulin, LDL-cholesterol, triglycerides and leptin and were positively related to HDL-cholesterol. Reduced circulating omentin levels could play a role in the etiopathogenesis of obesity and T2DM. The increase in circulating omentin levels and the decrease in omentin mRNA expression in SCAT of obese women after LSG might contribute to surgery-induced metabolic improvements and sustained reduction of body weight.
    Physiological research / Academia Scientiarum Bohemoslovaca 01/2014; · 1.53 Impact Factor
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    ABSTRACT: 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.
    Cryobiology 01/2014; · 2.14 Impact Factor
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    ABSTRACT: Objective: The aim of our study was to analyze the results of oral glucose tolerant test (oGTT) of pregnant woman with currently used Czech criteria for diagnosis of GDM, to find out the prevalence of GDM if the measurement of glycemia in 1 hour of oGTT is included and to compare the prevalence of GDM using the new IADPSG (International Association of Diabetes and Pregnancy Study Groups) criteria versus the currently used Czech criteria. Design: Retrospective analysis.Settings: Department of Obstetrics and Gynecology of the First Faculty of Medicine and General Teaching Hospital, Prague.Methods: Data from the standard 75g 2-hour oral glucose tolerance test (oGTT) of 2567 pregnant females were analyzed using the currently recommended Czech cut-off values for plasma glucose at baseline and at2 hours of oGTT (5.6 and 7.7 mmol/l) and at baseline, 1 and2 hours oGTT (5.6, 8.9 and 7.7 mmol/l). The frequency of GDM using the Czech criteria was compared with the frequency of GDM using the novel IADPSG criteria (5.1, 10.0 and 8.5 mmol/l). Statistical analysis was done using the software GNU PSPP Statistical Analysis Software version 0.8.0-g0ad9f6.Results: When using the current Czech criteria (at baseline and 2 hours of oGTT) GDM was diagnosed in 362 (14.11%) females. Inclusion of glycemia at 1 hour of oGTT increased the frequency of GDM to 571 (22.26%) females (p<0.00). With the novel IADPSG criteria GDM was diagnosed in 818 (31.89%) females (p=0.038). 503 females i.e. 19.61% and 394 females i.e. 15.36% (when glycemia at 1 h of oGTT included) respectively met the IADPSG but not the Czech criteria and thus were not treated for GDM. In contrast, 47 (1.83%) resp. 147 (5.73%) of tested women who met the Czech but not the IADPSG criteria received unnecessary diabetes treatment. Conclusion: The frequency of GDM is higher with the novel IADPSG criteria when compared with the currently used Czech recommendation. Switching to IADPSG criteria might help unravel hitherto unidentified cases of GDM and thus improve outcomes for females with GDM and their offsprings. Keywords: gestational diabetes, oral glucose tolerant test, oGTT, Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study.
    Ceska gynekologie / Ceska lekarska spolecnost J. Ev. Purkyne 01/2014; 79(3):213-218.
  • Martin Haluzík, Štěpán Svačina
    Physiological research / Academia Scientiarum Bohemoslovaca 01/2014; 63 Suppl 2:ix-x. · 1.53 Impact Factor
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    ABSTRACT: Low-grade inflammation links obesity, insulin resistance, and cardiovascular diseases. We investigated the effects of laparoscopic sleeve gastrectomy (LSG) on expression profile of genes involved in inflammatory pathways in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM). At baseline, obese group had significantly increased mRNA expression of proinflammatory chemokines (CCL-3, -17, -22), chemokine receptor CCR1 and cytokines (IL-10, IL-18) in SCAT and chemokine and other proinflammatory receptors (CCR-1, -2, -3, TLR-2, -4) in PM relative to control group. LSG decreased body weight, improved metabolic profile and reduced mRNA expression of up-regulated chemokine receptors, chemokines and cytokines in SCAT. In contrast, expression profiles in PM were largely unaffected by LSG. We conclude that LSG improved proinflammatory profile in subcutaneous fat but not in peripheral monocytes. The sustained proinflammatory and chemotactic profile in PM even 2 years after LSG may contribute to partial persistence of metabolic complications in obese patients after metabolic surgery.
    Molecular and Cellular Endocrinology 11/2013; · 4.04 Impact Factor
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    ABSTRACT: Adipocyte fatty acid binding protein (A-FABP) is a novel adipokine involved in the regulation of lipid and glucose metabolism and inflammation. To evaluate its potential role in the development of postoperative hyperglycemia and insulin resistance we assessed A-FABP serum concentrations and mRNA expression in skeletal and myocardial muscle, subcutaneous and epicardial adipose tissue and peripheral monocytes in 11 diabetic and 20 age- and sex-matched non-diabetic patients undergoing elective cardiac surgery. Baseline serum A-FABP did not differ between the groups (31.1+/-5.1 vs. 25.9+/-4.6 ng/ml, p=0.175). Cardiac surgery markedly increased serum A-FABP in both groups with a rapid peak at the end of surgery followed by a gradual decrease to baseline values during the next 48 hours with no significant difference between the groups at any timepoint. These trends were analogous to postoperative excursions of plasma glucose, insulin and selected proinflammatory markers. Cardiac surgery increased A-FABP mRNA expression in peripheral monocytes, while no effect was observed in adipose tissue or muscle. Our data suggest that circulating A-FABP might be involved in the development of acute perioperative stress response, insulin resistance and hyperglycemia of critically ill irrespectively of the presence of diabetes mellitus.
    Physiological research / Academia Scientiarum Bohemoslovaca 11/2013; · 1.53 Impact Factor
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    ABSTRACT: Appropriate differentiation capacity of adipose tissue significantly affects its ability to store lipids and to protect nonadipose tissues against lipid spillover and development of insulin resistance. Preadipocyte factor-1 (Pref-1) is an important negative regulator of preadipocyte differentiation. The aim of our study was to explore the changes in circulating Pref-1 concentrations in female subjects with obesity (OB) (n=19), females with obesity and type 2 diabetes mellitus (T2DM) (n=22), and sex- and age-matched healthy control subjects (C) (n=22), and to study its modulation by very low calorie diet (VLCD), acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp, and 3 months' treatment with PPAR-α agonist fenofibrate. At baseline, serum Pref-1 concentrations were significantly higher in patients with T2DM compared to control group, while only nonsignificant trend towards higher levels was observed in OB group. 3 weeks of VLCD decreased Pref-1 levels in both OB and T2DM group, whereas 3 months of fenofibrate treatment had no significant effect. Hyperinsulinemia during the clamp significantly suppressed Pref-1 levels in both C and T2DM subjects and this suppression was unaffected by fenofibrate treatment. In a combined population of all groups, circulating Pref-1 levels correlated positively with insulin, leptin and glucose levels and HOMA (homeostasis model assessment) index. We conclude that elevated Pref-1 concentrations in T2DM subjects may contribute to impaired adipose tissue differentiation capacity associated with insulin resistance in obese patients with T2DM. The decrease of Pref-1 levels after VLCD may be involved in the improvement of metabolic status and the amelioration of insulin resistance in T2DM patients.
    Hormone and Metabolic Research 08/2013; · 2.15 Impact Factor
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    ABSTRACT: Hyperglycemia represents frequent adverse event reported in chronic myelogenous leukemia (CML) patients treated with nilotinib. In order to determine the major mechanism of glucose metabolism impairment, we performed a metabolic analysis using an oral glucose tolerance test as well as assessment of incretins and adipokines at baseline and after 3 months of nilotinib treatment in patients with CML. We proved that rapid insulin resistance, compensatory hyperinsulinaemia, and hypoadiponectinaemia develop after initiation of nilotinib therapy, which clarifies not only the mechanism of impaired glucose metabolism, but also explains the fast development of dyslipidaemia and peripheral artery occlusion in nilotinib-treated CML patients.
    Haematologica 05/2013; · 5.94 Impact Factor
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    ABSTRACT: PURPOSE: Serum procalcitonin (PCT) has become a routinely utilized parameter with a high prediction value of the severity of bacterial infectious complications and their immediate outcomes. Whereas the utility of PCT in differentiating between bacterial and viral infection is generally accepted, its significance in fungal infections has yet to be determined. The aim of the study was to determine the role of PCT testing in patients at high risk for invasive fungal infections. METHODS: Immunocompromised hematological patients undergoing cyclic chemotherapy treatment or allogeneic hemopoietic stem cell transplantation with infectious complications in which the infectious agents were identified during the disease course were evaluated. In patients with bacterial infection, positive hemocultures were documented, and in patients with fungal infection, the presence of either proven or probable disease was confirmed according to Ascioglu criteria. C-reactive protein (CRP) and PCT were prospectively assessed from the day following fever onset, for four consecutive days. RESULTS: Overall, 34 patients were evaluated, 21 with bacterial and 13 with fungal infections. Significant elevations of CRP concentrations (i.e., above the upper normal limit) were observed in all patients, with a tendency toward higher levels in bacterial (both gram-positive [Gr+] and Gr-negative [Gr-]) than in fungal infections. PCT levels were significantly elevated in patients with bacterial infections (e.g., predominantly in Gr- compared to Gr+), whereas in patients with fungal infections, we identified minimal or no PCT elevations, p < 0.01. For the fungal infections, according to constructed receiver operating characteristic curves, a combination of PCT <0.5 μg/L and CRP 100-300 mg/L offers the best specificity, sensitivity and positive and negative predictive values (81, 85, 73, and 89 %, respectively). CONCLUSION: Altogether, our data suggest that the finding of substantially elevated CRP combined with low PCT in immunocompromised patients may indicate systemic fungal infection. The use of this combination might simplify the diagnostic process, which otherwise can often be lengthy and arduous.
    Supportive Care in Cancer 05/2013; · 2.09 Impact Factor
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    ABSTRACT: OBJECTIVE: To assess the expression of the novel adipokine Fatty Acid Binding Protein-4 (FABP4) in synovial tissues, serum and the synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationships among FABP4, disease activity and metabolic status. METHODS: FABP4 levels were measured in the serum and synovial fluid of 40 patients with RA and 40 control patients with OA. The disease activity score (DAS28), C-reactive protein (CRP) levels and serum lipids were assessed in patients with RA. Immunohistochemical analysis and confocal microscopy were used to study the expression and cell-specific distribution of FABP4 in synovial tissues. RESULTS: The age, sex and body mass index (BMI) adjusted levels of FABP4 were significantly higher in the serum (p=0.001) and synovial fluid (p=0.005) of patients with RA when compared to OA patients. FABP4 levels were higher in females than in males and correlated positively with body mass index (BMI) in patients with RA. Independent of confounders, FABP4 levels correlated with total cholesterol and LDL cholesterol in patients with RA, but not in OA patients. FABP4 levels were not affected by disease activity. Furthermore, the increased expression of FABP4 that was otherwise restricted to synovial fibroblasts, macrophages and B-cells was noted in RA patients at levels higher than that observed in OA patients. CONCLUSIONS: The observed elevation of FABP4 levels in RA patients and the positive correlation of the adipokine to cholesterol suggest that FABP4 may represent a potential link between RA and the increased risk of atherosclerotic changes.
    Cytokine 05/2013; · 2.52 Impact Factor
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    ABSTRACT: Ghrelin and agonists of its receptor GHS-R1a are potential substances for the treatment of cachexia. In the present study, we investigated the acute and long term effects of the GHS R1a agonist JMV 1843 (H Aib-DTrp-D-gTrp-CHO) on food intake, body weight and metabolic parameters in lean C57BL/6 male mice. Additionally, we examined stability of JMV 1843 in mouse blood serum. A single subcutaneous injection of JMV 1843 (0.01-10 mg/kg) increased food intake in fed mice in a dose-dependent manner, up to 5-times relative to the saline-treated group (ED(50) = 1.94 mg/kg at 250 min). JMV 1843 was stable in mouse serum in vitro for 24 hours, but was mostly eliminated from mouse blood after 2 hours in vivo. Ten days of treatment with JMV 1843 (subcutaneous administration, 10 or 20 mg/kg/day) significantly increased food intake, body weight and mRNA expression of the orexigenic neuropeptide Y and agouti-related peptide in the medial basal hypothalamus and decreased the expression of uncoupling protein 1 in brown adipose tissue. Our data suggest that JMV 1843 could have possible future uses in the treatment of cachexia.
    Physiological research / Academia Scientiarum Bohemoslovaca 04/2013; · 1.53 Impact Factor
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    ABSTRACT: Context:Catecholamine overproduction in pheochromocytoma affects basal metabolism, resulting in weight loss despite normal food intake.Objective:The objective of the study was to evaluate changes in energy metabolism expressed as resting energy expenditure (REE) in patients with pheochromocytoma before and after adrenalectomy and the possible relationship with circulating inflammatory markers.Design:We measured REE in 17 patients (8 women) with pheochromocytoma by indirect calorimetry (Vmax-Encore 29N system) before and 1 year after adrenalectomy. Body fat percentage was measured with a Bodystat device. Inflammatory markers (leukocytes count and C-reactive protein) and cytokines (TNF-α, IL-6, and IL-8) were analyzed with a Luminex 200.Results:REE measured in the pheochromocytoma group was 10.4% higher than the predicted value (1731 ± 314 vs 1581 ± 271 kcal/d; P = .004). Adrenalectomy significantly increased body mass index (P =0.004) and the percentage of body fat (P = .01), with a proportional increase in fat distribution (waist circumference, P = .045; hip circumference, P = .001). REE significantly decreased after adrenalectomy (1731 ± 314 vs 1539 ± 215 kcal/d; P = .002), even after adjustments in body surface and body weight (P < .001). After adrenalectomy, we found a significant decrease in leukocyte counts (P = .014) and in the levels of TNF-α (P < .001), IL-6 (P = .048), and IL-8 (P = .007) but not C-reactive protein (P = .09). No significant correlations among calorimetry parameters, hormones, and proinflammatory markers were detected.Conclusions:Chronic catecholamine overproduction in pheochromocytoma may lead to a proinflammatory and hypermetabolic state characterized by increased REE. Adrenalectomy leads to the normalization of energy metabolism followed by an increase in body mass index and body fat content and decreases in inflammatory markers and cytokines.
    The Journal of clinical endocrinology and metabolism 02/2013; · 6.50 Impact Factor
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    ABSTRACT: Objective:Recent studies linked circulating pigment epithelium-derived factor (PEDF) to obesity-associated insulin resistance, but the main source of circulating PEDF is unknown. We aimed to investigate liver and adipose tissue PEDF gene expression in association with obesity and insulin resistance.Design, subjects and methods:Three (two cross-sectional and one longitudinal) independent cohorts have been studied, for adipose tissue (n=80 and n=30) and liver gene expression (n=32 and n=14). Effects of high glucose and cytokines on HepG2 cell line were also investigated. PEDF gene expression and circulating PEDF were analyzed using real-time PCR and ELISA, respectively.Results:In a first cohort of subjects, PEDF relative gene expression was higher in subcutaneous (SC) than in omental (OM) adipose tissue (P<0.0001) being also higher in mature adipocytes compared with stromo-vascular cells (P<0.0001). However, OM PEDF relative gene expression was decreased in morbidly obese subjects (P=0.01). Both OM PEDF and OM PEDF receptor (PEDFR) correlated positively with lipogenic and lipolytic genes, and with genes implicated in the lipid vacuole formation. Circulating PEDF levels were not associated with fat PEDF gene expression. In the second cohort, SC PEDF was decreased in subjects with type 2 diabetes and did not change significantly after weight loss. We next explored circulating PEDF in association with markers of liver-related insulin resistance injury (alanine aminotransferase, r=0.59, P=0.001). Interestingly, liver PEDF gene expression increased with obesity and insulin resistance in men, being significantly associated with fasting glucose and glycated hemoglobin in two independent cohorts. In fact, high glucose led to increased PEDF in HepG2 cells, while inflammatory stimuli present in the adipose tissue environment downregulated PEDF.Conclusion:Liver, but not adipose tissue, might be the source of increased circulating PEDF linked to insulin resistance.International Journal of Obesity advance online publication, 15 January 2013; doi:10.1038/ijo.2012.223.
    International journal of obesity (2005) 01/2013; · 5.22 Impact Factor

Publication Stats

3k Citations
491.15 Total Impact Points

Institutions

  • 1995–2014
    • Charles University in Prague
      • • Department of Normal, Pathological and Clinical Physiology (3. LF)
      • • 1. lékařská fakulta
      • • Klinika dětského a dorostového lékařství (1. LF)
      • • Gynekologicko-porodnická klinika (1. LF)
      • • Ústav patologické fyziologie (Plzeň)
      Praha, Praha, Czech Republic
  • 2011
    • Institute for Clinical and Experimental Medicine (IKEM)
      Praha, Praha, Czech Republic
  • 2006–2011
    • Revmatologicky Ustav
      Praha, Praha, Czech Republic
  • 2002–2011
    • National Institutes of Health
      • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      Maryland, United States
  • 2009
    • Medical University of Graz
      • Clinical Institute of Medical and Chemical Laboratory Diagnostics
      Gratz, Styria, Austria
  • 2007–2009
    • University General Hospital
      Houston, Texas, United States
    • University of Cambridge
      • Department of Paediatrics
      Cambridge, ENG, United Kingdom
  • 2008
    • Technische Universität Dresden
      • Center for Internal Medicine
      Dresden, Saxony, Germany
  • 2007–2008
    • Center for Individual Care
      Praha, Praha, Czech Republic
  • 1995–2008
    • The Police Academy of the Czech Republic in Prague
      Praha, Praha, Czech Republic
  • 2001
    • Institute of Endocrinology
      Praha, Praha, Czech Republic