M Haluzík

Charles University in Prague, Praha, Praha, Czech Republic

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Publications (220)564.23 Total impact

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    ABSTRACT: Objectives Obesity is a frequent metabolic disorder but an effective therapy is still scarce. Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity but are ineffective after peripheral application. We have designed lipidized analogs of prolactin-releasing peptide (PrRP) which is involved in energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice.ResultsLipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF (NPFF)-2 receptor. Peripheral administration of myristoylated and palmitoylated PrRP analogs to fasted mice induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated-PrRP31 and myristoylated-PrRP20 lowered food intake, body weight and improved metabolic parameters and attenuated lipogenesis in mice with diet-induced obesity.Conclusions Our data suggest that the lipidization of PrRP enhances stability and mediates its effect in central nervous system. Strong anorexigenic and body-weight-reducing effects make lipidized PrRP an attractive candidate for anti-obesity treatment.International Journal of Obesity accepted article preview online, 16 March 2015. doi:10.1038/ijo.2015.28.
    International journal of obesity (2005) 03/2015; DOI:10.1038/ijo.2015.28 · 5.22 Impact Factor
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    ABSTRACT: Numerous epidemiological and experimental studies have demonstrated that patients who suffer from metabolic disorders, such as type 2 diabetes mellitus (T2DM) or obesity, have higher risks of cognitive dysfunction and of Alzheimer's disease (AD). Impaired insulin signaling in the brain could contribute to the formation of neurofibrillary tangles, which contain an abnormally hyperphosphorylated tau protein. This study aimed to determine whether potential tau hyperphosphorylation could be detected in an obesity-induced pre-diabetes state and whether anorexigenic agents could affect this state. We demonstrated that 6-month-old mice with monosodium glutamate (MSG) obesity, which represent a model of obesity-induced pre-diabetes, had increased tau phosphorylation at Ser396 and Thr231 in the hippocampus compared with the controls, as determined by western blots. Two weeks of subcutaneous treatment with a lipidized analog of prolactin-releasing peptide (palm-PrRP31) or with the T2DM drug liraglutide, which both had a central anorexigenic effect, resulted in increased phosphorylation of the insulin cascade kinases PDK1 (Ser241), Akt (Thr308), and GSK-3β (Ser9). Furthermore, these drugs attenuated phosphorylation at Ser396, Thr231, and Thr212 of tau and of the primary tau kinases in the hippocampi of 6-month-old MSG-obese mice. We identified tau hyperphosphorylation in the obesity-induced pre-diabetes state in MSG-obese mice and demonstrated the beneficial effects of palm-PrRP31 and liraglutide, both of known central anorexigenic effects, on hippocampal insulin signaling and on tau phosphorylation.
    Journal of Alzheimer's disease: JAD 01/2015; DOI:10.3233/JAD-143150 · 3.61 Impact Factor
  • Martin Haluzík, Miloš Mráz, Stěpán Svačina
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    ABSTRACT: Incretin-based therapies either increase endogenous levels of glucagon-like peptide-1 by prolonging its half-life (DPP-4 inhibitors) or directly stimulate its receptor (glucagon-like peptide-1 analogues; GLP-1 RA). They are currently widely used for the treatment of patients with type 2 diabetes mellitus owing to good antidiabetic efficacy, low risk of hypoglycemia, and relatively few other side effects. They also offer potential additional benefits such as weight neutrality or weight loss, positive effects on blood pressure and lipid levels, and potential cardio- and neuroprotectivity. Some experimental and clinical studies have raised concerns with respect to potential cardiovascular and pancreatic side effects of these therapies such as increased risk of heart failure with DPP-4 inhibitors as well as acute pancreatitis and pancreatic cancer with both classes. The available data are at present not robust enough to enable firm conclusions regarding these potential associations. Nevertheless, some recent data suggest a possibility of slightly increased risk of acute pancreatitis with GLP-1 RAs while they do not indicate increased risk of pancreatic cancer. Ongoing cardiovascular outcome trials will shed more light on the possible cardioprotective effects of incretin-based therapies as well as on the possible interconnection of DPP-4 inhibitors and heart failure.
    Drug Safety 11/2014; DOI:10.1007/s40264-014-0238-8 · 2.62 Impact Factor
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of a metabolic syndrome. To date, liver biopsy has been the gold standard used to differentiate between simple steatosis and steatohepatitis/fibrosis. Our aim was to compare the relevance of serum non-invasive parameters and scoring systems in the staging of liver fibrosis and non-alcoholic steatohepatitis (NASH) in patients with NAFLD.
    PLoS ONE 10/2014; 9(10):e111551. DOI:10.1371/journal.pone.0111551 · 3.53 Impact Factor
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    ABSTRACT: The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25%; 75%) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs 1.71 (1.12; 7.08) ug · l(-1) and transiently decreased immediately after fasting: 3.45 ug · l(-1) (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs 3.50 (2.46; 6.30) · l0(3) and transiently increased immediately after fasting: 2.22 (1.26; 3.24) · l0(3), (P< 0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet.
    Nutrition 10/2014; 30(10):1223. DOI:10.1016/j.nut.2014.07.021 · 3.05 Impact Factor
  • 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.
    Journal of Endocrinology 07/2014; 222(3). DOI:10.1530/JOE-14-0283 · 3.59 Impact Factor
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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; DOI:10.1016/j.mce.2014.06.003 · 4.24 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. · 1.49 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; · 1.49 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; DOI:10.1177/1932296814533847
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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 04/2014; DOI:10.1016/j.cryobiol.2014.02.007 · 1.64 Impact Factor
  • Martin Haluzik
    Journal of Endocrinology 03/2014; 221(1):E1-2. DOI:10.1530/JOE-14-0056 · 3.59 Impact Factor
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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. DOI:10.5114/wiitm.2014.40387 · 1.09 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Martin Haluzik, Denisa Haluziková
    Expert Review of Endocrinology &amp Metabolism 01/2014; 6(1). DOI:10.1586/eem.10.69
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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; · 1.49 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. · 1.49 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; DOI:10.1016/j.mce.2013.11.013 · 4.24 Impact Factor
  • Nutrition 11/2013; 29(s 11–12):1435–1436. DOI:10.1016/j.nut.2013.07.007 · 3.05 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; · 1.49 Impact Factor

Publication Stats

4k Citations
564.23 Total Impact Points

Institutions

  • 1995–2015
    • Charles University in Prague
      • • 1st Faculty of Medicine
      • • Department of Internal Medicine (2. LF)
      • • Klinika dětského a dorostového lékařství (1. LF)
      • • Gynekologicko-porodnická klinika (1. LF)
      • • Ústav patologické fyziologie (Plzeň)
      Praha, Praha, Czech Republic
  • 2011–2012
    • Fakultní nemocnice Královské Vinohrady
      Praha, Praha, Czech Republic
    • Institute for Clinical and Experimental Medicine (IKEM)
      Praha, Praha, Czech Republic
  • 2006–2011
    • Revmatologicky Ustav
      Praha, Praha, Czech Republic
  • 2003–2011
    • National Institutes of Health
      • • Section on Molecular and Cell Biology
      • • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      Maryland, United States
  • 2009
    • University General Hospital
      Houston, Texas, United States
  • 2006–2009
    • Medical University of Graz
      • Clinical Institute of Medical and Chemical Laboratory Diagnostics
      Gratz, Styria, Austria
  • 2008
    • Technische Universität Dresden
      • Center for Internal Medicine
      Dresden, Saxony, Germany
  • 1995–2008
    • The Police Academy of the Czech Republic in Prague
      Praha, Praha, Czech Republic
  • 2007
    • Center for Individual Care
      Praha, Praha, Czech Republic
    • University of Cambridge
      • Department of Paediatrics
      Cambridge, ENG, United Kingdom
  • 2004
    • National Institute of Mental Health (NIMH)
      베서스다, Maryland, United States
    • University of Toronto
      Toronto, Ontario, Canada
  • 2002
    • National Cancer Institute (USA)
      • Metabolism Branch
      베서스다, Maryland, United States
    • Yale University
      • Department of Cellular and Molecular Physiology
      New Haven, Connecticut, United States
  • 2001
    • Institute of Endocrinology
      Praha, Praha, Czech Republic