OBJECTIVE: 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. DESIGN AND METHODS: Seventeen females with obesity undergoing LSG and 15 lean healthy females were included into the study. Anthropometric and biochemical parameters, serum concentrations of FGF-19 and -21, insulin, adiponectin, leptin, C-reactive protein, resistin, amylin (total), ghrelin (active), glucagon-like peptide 1 (GLP-1, active), glucose-dependent insulinotropic peptide (GIP, total), peptide YY (PYY, total), pancreatic polypeptide (PP), and bile acids, and mRNA expression of selected adipokines and inflammatory markers in bioptic samples of subcutaneous fat were assessed at baseline and 6, 12, and 24 months after LSG. RESULTS: LSG markedly decreased body weight, BMI, waist circumference, and insulin levels and improved systemic inflammation and lipid levels. FGF-19 concentrations increased and FGF-21 concentrations decreased after LSG along with increased adiponectin and decreased leptin, amylin, and ghrelin levels. GLP-1, GIP, PP, and circulating bile acids were not affected by LSG. PYY decreased significantly 24 months after surgery only. mRNA expression analysis in subcutaneous fat showed markedly reduced proinflammatory state. CONCLUSIONS: Our results indicate that increased FGF-19 and decreased ghrelin concentrations could have partially contributed to the improvement of systemic inflammation and some metabolic parameters after LSG, while changes of FGF-21 are rather secondary because of weight loss.

• MeSH
• adiponektin krev   MeSH
• amylin krev   MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• fibroblastové růstové faktory krev   MeSH
• gastrektomie metody   MeSH
• ghrelin krev   MeSH
• glukagonu podobný peptid 1 krev   MeSH
• hmotnostní úbytek MeSH
• index tělesné hmotnosti MeSH
• inzulin krev   MeSH
• inzulinová rezistence MeSH
• leptin krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• morbidní obezita krev   chirurgie   MeSH
• obvod pasu MeSH
• pankreatický polypeptid krev   MeSH
• peptid YY krev   MeSH
• podkožní tuk metabolismus   MeSH
• prospektivní studie MeSH
• resistin krev   MeSH
• žaludeční inhibiční polypeptid krev   MeSH
• žlučové kyseliny a soli krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adiponektin MeSH
• amylin MeSH
• C-reaktivní protein MeSH
• FGF19 protein, human MeSH Prohlížeč
• fibroblast growth factor 21 MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• ghrelin MeSH
• glukagonu podobný peptid 1 MeSH
• inzulin MeSH
• leptin MeSH
• messenger RNA MeSH
• pankreatický polypeptid MeSH
• peptid YY MeSH
• resistin MeSH
• žaludeční inhibiční polypeptid MeSH
• žlučové kyseliny a soli MeSH

BACKGROUND: The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. We investigated the effect of different bariatric procedures on circulating FGF-19 levels and the resulting impact on mitochondrial health in white adipose tissue (AT). METHODS: Obese and type-2 diabetic women (n = 39, BMI > 35 kg/m2) undergoing either biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) participated in this ethics approved study. Anthropometry, biochemical, clinical data, serum, and AT biopsies were collected before and 6 months after surgery. Mitochondrial gene expression in adipose biopsies and serum FGF-19 levels were then assessed. RESULTS: All surgeries led to metabolic improvements with BPD producing the greatest benefits on weight loss (↓30%), HbA1c (↓28%), and cholesterol (↓25%) reduction, whilst LGCP resulted in similar HbA1c improvements (adjusted for BMI). Circulating FGF-19 increased in both BPD and LGCP (χ2(2) = 8.088; P = 0.018), whilst, in LAGB, FGF-19 serum levels decreased (P = 0.028). Interestingly, circulating FGF-19 was inversely correlated with mitochondrial number in AT across all surgeries (n = 39). In contrast to LGCP and LAGB, mitochondrial number in BPD patients corresponded directly with changes in 12 of 14 mitochondrial genes assayed (P < 0.01). CONCLUSIONS: Elevated serum FGF-19 levels post-surgery were associated with improved mitochondrial health in AT and overall diabetic remission. Changes in circulating FGF-19 levels were surgery-specific, with BPD producing the best metabolic outcomes among the study procedures (BPD > LGCP > LAGB), and highlighting mitochondria in AT as a potential target of FGF-19 during diabetes remission.

• Klíčová slova
• Bariatric surgery, FGF-19, Gut hormone, Mitochondria, Obesity, Type-2 diabetes recovery,
• MeSH
• bariatrická chirurgie metody   MeSH
• diabetes mellitus 2. typu metabolismus   patologie   MeSH
• dospělí MeSH
• fibroblastové růstové faktory metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• obezita metabolismus   patologie   terapie   MeSH
• prospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• FGF19 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH

Background: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention. Methods: The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 and <7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes. Age-matched controls comprised healthy pregnant and non-pregnant women. In addition to adipokines, clinical parameters and measures of glucose control were assessed. Results: Women with GDM (n = 23) had significantly lower adiponectin and higher A-FABP levels compared to healthy pregnant (n = 29) or non-pregnant (n = 25) controls, while no significant differences in FGF-19 between the groups were found. The therapeutic intervention shifted adiponectin and A-FABP levels in GDM women towards concentrations of healthy pregnant controls. Adipokines were associated with visceral adiposity and glucose control. Conclusion: Women with GDM showed altered adipokine production even in the first trimester of pregnancy. Early therapeutic intervention not only improved glucose control but also normalized impaired adipokine production.

• Klíčová slova
• adipocyte fatty acid-binding protein, adiponectin, fibroblast growth factor-19, gestational diabetes,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Since fibroblast growth factor 19 (FGF-19) is a potent metabolic regulator that influences glucose and lipid homeostasis, our aim was to develop an ELISA assay for measuring FGF-19 in human serum and to investigate its concentrations in healthy volunteers and patients suffering from metabolic syndrome. MATERIAL AND METHODS: A sandwich ELISA method was developed for quantitative determination of human FGF-19 in serum samples. Blood pressure, waist circumference, FGF-21 serum levels, serum cholesterol, triacylglycerols, HDL-cholesterol, LDL-cholesterol, insulin, glucose, adiponectin, uric acid, creatinine, hs-CRP and calculated BMI and Quicki insulin sensitivity index were measured in 153 healthy volunteers and 66 persons with metabolic syndrome. RESULTS: Neither sex nor age influenced FGF-19 serum concentration in the healthy volunteers. Probands with metabolic syndrome had 65 % lower FGF-19 serum values than the healthy ones (medians 158.6 versus 242.4 ng/L; p<0.01). FGF-19 correlated with glucose (r = -0.35, p<0.01), HDL (r = 0.24, p = 0.045), triacylglycerols (r = -0.19, p = 0.05) and with a number of other risk factors for metabolic syndrome (r = -0.28, p = 0.01). When adjusted to the concentrations of triacylglycerols, BMI and glucose, and finally to all data pertinent to FGF-19 (according to correlation analysis), our data indicate that FGF-19 is an independent marker of metabolic syndrome. CONCLUSIONS: The present study demonstrates the analytical properties of the ELISA FGF-19 assay and its usefulness when studying the metabolic syndrome. Serum concentrations of FGF-19 could be new key predictors of metabolic syndrome and thereby even a new negative risk factor of atherosclerosis.

• MeSH
• diabetes mellitus 2. typu krev   MeSH
• ELISA metody   MeSH
• fibroblastové růstové faktory analýza   MeSH
• lidé MeSH
• metabolický syndrom krev   MeSH
• rekombinantní proteiny analýza   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• FGF19 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• rekombinantní proteiny MeSH

The aim of our study was to measure serum concentrations of fibroblast growth factor 19 (FGF-19) in patients with obesity (OB), obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C) at baseline and after selected interventions. We measured serum FGF-19 levels and other biochemical and hormonal parameters in 29 OB and 19 T2DM females and 30 sex- and age-matched control subjects. The interventions were acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp (n=11 for T2DM and 10 for C), very-low calorie diet (VLCD, n=12 for OB) and 3 months treatment with PPAR-alpha agonist fenofibrate (n=11 for T2DM). Baseline serum FGF-19 levels were significantly lower in OB relative to C group (132.1+/-12.7 vs. 202.2+/-16.7 pg/ml, p<0.05), while no significant difference was observed between T2DM and OB or control group. Acute hyperinsulinemia tended to decrease FGF-19 levels in both healthy and T2DM subjects. Three weeks of VLCD in OB group had no significant effect on FGF-19, whereas three months of fenofibrate treatment markedly reduced FGF-19 levels in T2DM patients (194.58+/-26.2 vs. 107.47+/-25.0 pg/ml, p<0.05). We conclude that FGF-19 levels in our study were at least partially dependent upon nutritional status, but were not related to parameters of glucose metabolism or insulin sensitivity.

• MeSH
• akutní nemoc MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu krev   terapie   MeSH
• dospělí MeSH
• fenofibrát farmakologie   terapeutické užití   MeSH
• fibroblastové růstové faktory krev   MeSH
• hyperinzulinismus krev   terapie   MeSH
• inzulinová rezistence MeSH
• kalorická restrikce * metody   MeSH
• krevní glukóza metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita krev   MeSH
• PPAR alfa agonisté   fyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• biologické markery MeSH
• fenofibrát MeSH
• FGF19 protein, human MeSH Prohlížeč
• fibroblastové růstové faktory MeSH
• krevní glukóza MeSH
• PPAR alfa MeSH

INTRODUCTION: Laparoscopic greater curvature plication (LGCP) is a novel restrictive technique that reduces gastric volume by plication of the greater curvature. The advantage of LGCP is its reversibility in comparison to laparoscopic sleeve gastrectomy. Nowadays, the long-term LGCP efficacy, safety and metabolic effect are being investigated. AIM: To assess body composition, clinical complications and metabolic changes in obese patients 6 and 12 months after laparoscopic greater curvature plication. MATERIAL AND METHODS: A total of 70 subjects underwent LGCP; 52 of them (33 women and 19 men) completed 1-year follow-up study. Anthropometry and biochemical parameters (glucose, glycated haemoglobin, lipids, ghrelin, leptin, adiponectin and fibroblast growth factor 21 [FGF-21]) were assessed before and 3, 6, and 12 months after surgery. RESULTS: All study participants exhibited statistically significant weight loss at both 6 and 12 months following the LGCP compared to baseline, with significant reductions in body composition - body weight, body mass index, percentage excess weight loss (%EWL), and percentage excess BMI loss (%EBL) (p ≤ 0.001). Moreover, significant lowering of glucose and glycated haemoglobin, triacylglycerols and leptin was observed 12 months after LGCP. On the other hand, plasma concentrations of ghrelin, adiponectin and LDL cholesterol increased significantly. Total cholesterol, LDL cholesterol and FGF-21 levels did not change significantly. CONCLUSIONS: Laparoscopic greater curvature plication appears to be a procedure with good restriction results, which might be mediated through alteration in incretin metabolism. Technical aspects and standardization of the procedure still remain to be worked out.

• Klíčová slova
• fibroblast growth factor 21, gastric plication, ghrelin, metabolic effect, weight loss,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Nodular melanoma is one of the most life threatening tumors with still poor therapeutic outcome. Similarly to other tumors, permissive microenvironment is essential for melanoma progression. Features of this microenvironment are arising from molecular crosstalk between the melanoma cells (MC) and the surrounding cell populations in the context of skin tissue. Here, we study the effect of melanoma cells on human primary keratinocytes (HPK). Presence of MC is as an important modulator of the tumor microenvironment and we compare it to the effect of nonmalignant lowly differentiated cells also originating from neural crest (NCSC). METHODS: Comparative morphometrical and immunohistochemical analysis of epidermis surrounding nodular melanoma (n = 100) was performed. Data were compared to results of transcriptome profiling of in vitro models, in which HPK were co-cultured with MC, normal human melanocytes, and NCSC, respectively. Differentially expressed candidate genes were verified by RT-qPCR. Biological activity of candidate proteins was assessed on cultured HPK. RESULTS: Epidermis surrounding nodular melanoma exhibits hyperplastic features in 90% of cases. This hyperplastic region exhibits aberrant suprabasal expression of keratin 14 accompanied by loss of keratin 10. We observe that MC and NCSC are able to increase expression of keratins 8, 14, 19, and vimentin in the co-cultured HPK. This in vitro finding partially correlates with pseudoepitheliomatous hyperplasia observed in melanoma biopsies. We provide evidence of FGF-2, CXCL-1, IL-8, and VEGF-A participation in the activity of melanoma cells on keratinocytes. CONCLUSION: We conclude that the MC are able to influence locally the differentiation pattern of keratinocytes in vivo as well as in vitro. This interaction further highlights the role of intercellular interactions in melanoma. The reciprocal role of activated keratinocytes on biology of melanoma cells shall be verified in the future.

• MeSH
• buněčná diferenciace * genetika   MeSH
• chemokin CXCL1 farmakologie   MeSH
• dospělí MeSH
• epidermální buňky * MeSH
• epidermis patologie   MeSH
• fibroblastový růstový faktor 2 farmakologie   MeSH
• interleukin-8 farmakologie   MeSH
• keratin-10 metabolismus   MeSH
• keratin-14 metabolismus   MeSH
• keratinocyty cytologie   účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanocyty metabolismus   MeSH
• melanom metabolismus   patologie   MeSH
• metastázy nádorů MeSH
• mezibuněčná komunikace * MeSH
• nádorové buněčné linie MeSH
• proteiny S100 metabolismus   MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• vaskulární endoteliální růstový faktor A farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemokin CXCL1 MeSH
• fibroblastový růstový faktor 2 MeSH
• interleukin-8 MeSH
• keratin-10 MeSH
• keratin-14 MeSH
• proteiny S100 MeSH
• vaskulární endoteliální růstový faktor A MeSH

The aim of this study was to evaluate the role of proangiogenic growth factors in an experimental model of ischemia/reperfusion injury (I/R) in both normotensive and hypertensive rats. Renal ischemic injury was induced in transgenic rats rendered hypertensive due to renin overproduction [TGR (mREN-2)-27] and in normotensive Hannover Sprague-Dawley rats (HanSD). Animals were treated for 12 weeks with either tacrolimus (TAC, 0.1 mg/kg per day, intramuscularly [IM]) or placebo. After 12 weeks, kidneys were harvested for morphologic, immunohistochemical, and RT-PCR analysis. Both normotensive and hypertensive untreated rats developed significantly greater proteinuria and glomerulosclerosis compared with TAC-treated rats. Immunohistologically, TGR showed higher basic fibroblast growth factor (bFGF) protein expression compared with normotensive HanSD. TAC-treated rats had higher bFGF protein expression than untreated rats. Vascular endothelial growth factor (VEGF) protein expression in glomeruli was more increased in TGR after I/R than in sham-operated animals. TAC-treated TGR hosts developed higher VEGF mRNA expression compared with both untreated and sham groups; however, there were no differences between treated and untreated normotensive HanSD animals. bFGF is involved in the fibrogenesis induced by hypertension and I/R injury. The nature of the increase in proangiogeneic growth factor expression among tacrolimus-treated animals remains to be elucidated.

• MeSH
• fibroblastový růstový faktor 2 genetika   MeSH
• geneticky modifikovaná zvířata MeSH
• hypertenze patofyziologie   MeSH
• krevní tlak MeSH
• krysa rodu Rattus MeSH
• ledviny * MeSH
• modely nemocí na zvířatech MeSH
• patologická angiogeneze prevence a kontrola   MeSH
• potkani Sprague-Dawley MeSH
• reperfuzní poškození patologie   MeSH
• takrolimus terapeutické užití   MeSH
• transplantace ledvin imunologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fibroblastový růstový faktor 2 MeSH
• takrolimus MeSH