Tobias Tatarczyk

Monocyte migration : A novel effect and signaling pathways of catestatin

Several members of the neuropeptide family exert chemotactic actions on blood monocytes consistent with neurogenic inflammation. Furthermore, chromogranin A (CgA) containing Alzheimer plaques are characterized by extensive microglia activation and such activation induces neuronal damage. We therefore hypothesized that the catecholamine release inhibitory peptide catestatin (hCgA(352-372)) would induce directed monocyte migration. We demonstrate that catestatin dose-dependently stimulates chemotaxis of human peripheral blood monocytes, exhibiting its maximal effect at a concentration of 1 nM comparable to the established chemoattractant formylated peptide Met-Leu-Phe (fMLP). The naturally occurring catestatin variants differed in their chemotactic property insofar as that the Pro370Leu variant was even more potent than wild type, whereas the Gly364Ser variant was less effective. Specificity of this effect was shown by inhibition of catestatin-induced chemotaxis by a specific neutralizing antibody. In addition, catestatin mediated effect was blocked by dimethylsphingosine and treatment with endothelial differentiation gene (Edg)-1 and Edg-3 antisense RNA as well as by incubation with pertussis toxin and genistein indicating involvement of tyrosine kinase receptor-, G-protein- and sphingosine-1-phosphate signaling. Catestatin also stimulated Akt- and extracellular signal related kinase (ERK)-phosphorylation and catestatin-induced chemotaxis was blocked by blockers of phosphoinositide-3 (PI-3) kinase and nitric oxide as well as by inhibition of the mitogen-activated protein kinases (MAPK) system indicating involvement of these signal transduction pathways. In summary, our data indicate that catestatin induces monocyte chemotaxis by activation of a variety of signal transduction pathways suggesting a role of this peptide as an inflammatory cytokine.

Effects of pronounced weight loss on Adiponectin oligomer composition and metabolic parameters

Objective: Adiponectin is an adipocytokine secreted into circulation in three isoforms. The aim of the study was to investigate changes of adiponectin isoforms during profound weight loss and its relation to anthropomorphometric and metabolic parameters.

Are plasma VEGF and its soluble receptor sFlt-1 atherogenic risk factors? Cross-sectional data from the SAPHIR study.

AIMS Vascular endothelial growth factor (VEGF) is a potent hypoxia-regulated angiogenic factor. Its soluble receptor soluble (s)Flt-1 binds VEGF with high affinity inhibiting the angiogenic function of VEGF. The role of circulating VEGF in atherosclerosis is unclear. METHODS AND RESULTS In 909 healthy subjects (511 male, 398 female) from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) we determined fasting plasma VEGF and sFlt-1 concentration, cardiovascular risk factors and carotid atherosclerosis. VEGF levels were lower and sFlt-1 levels higher in men than in women. VEGF and sFlt-1 showed a positive correlation. In the entire population VEGF correlated positively with age, BMI, insulin resistance, white blood cell and platelet count, C-reactive protein (CRP) and carotid intima media thickness (IMT). After adjustment for age, VEGF showed a weak positive correlation with BMI, liver enzymes, CRP and platelet count in males. In females VEGF correlated negatively with LDL-cholesterol and positively with insulin resistance and platelet count. After adjustment for age, no significant correlation with carotid atherosclerosis could be detected. CONCLUSION Plasma VEGF and sFlt-1 are only weakly correlated with cardiovascular risk factors, suggesting that circulating VEGF levels do have only a minor impact on the development of atherosclerosis.

The Taq1B-variant in the cholesteryl ester-transfer protein gene and the risk of metabolic syndrome.

The metabolic syndrome is associated with low high‐density lipoprotein–cholesterol (HDL‐C) and decreased low‐density lipoprotein (LDL) particle size. The Taq1B‐polymorphism in the cholesteryl ester–transfer protein (CETP)‐gene influences HDL‐C, CETP concentration, and LDL‐size. We investigated the effect of the Taq1B‐polymorphism on the risk of the metabolic syndrome in 1,503 participants (973 men, 530 women) of the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk study. CETP concentration was determined in a subgroup (n = 486) by an enzyme‐linked immunosorbent assay. Prevalence of the metabolic syndrome was 16.7% (18.5% in men, 13.5% in women). The Taq1B‐polymorphism influenced significantly CETP concentrations, HDL‐C levels, and LDL‐size (P < 0.001 for all). The relative risk of the metabolic syndrome was reduced by 32% (odds ratio (OR) 0.68 (95% CI: 0.51–0.89), P = 0.005) in carriers of the B2 variant. This risk reduction persisted after adjustment for age and sex (OR 0.69 (0.53–0.92), P = 0.01) and after further adjustment for body mass index, waist‐to‐hip ratio, blood pressure, insulin resistance (IR), HDL‐C, and triglycerides (TGs) (OR 0.43 (0.26–0.72), P = 0.001). Furthermore, the risk reduction was more pronounced in men than in women. We conclude that CETP plays an important role in the metabolic syndrome, possibly involving novel functions of CETP.

Chronic antiepileptic monotherapy, bone metabolism, and body composition in non-institutionalized children.

Aim  The aim of this study was to determine the influence of chronic monotherapy with antiepileptic drugs (AEDs) on vitamin D levels, bone metabolism, and body composition.

A-FABP—A Biomarker Associated With the Metabolic Syndrome and/or an Indicator of Weight Change?

Objective: Adipocyte fatty acid‐binding protein (A‐FABP) is a plasma biomarker recently associated with the metabolic syndrome. The aim of these studies was to investigate changes of A‐FABP during profound weight loss induced by laparoscopic adjustable gastric banding (LAGB).

Analysis of long-chain ω-3 fatty acid content in fish-oil supplements

ZusammenfassungHINTERGRUND: In zahlreichen Studien wurden die verschiedensten vorteilhaften Effekte von mehrfach ungesättigten Omega 3 Fettsäuren auf Atherosklerose, Arrhythmie und Hypertriglyzeridämie nachgewiesen, was zahlreiche Gesundheitsorganisationen dazu veranlasst hat, einen täglichen Verzehr von einem Gramm Omega 3 Fettsäuren täglich für antiatherosklerotische sowie antiarrhytmische Wirkungen oder zwei bis vier g/d Omega 3 Fettsäuren zur Senkung der Plasmatriglyzeride zu empfehlen. Es sind zahlreiche Präparate auf dem Markt erschienen, welche die ω-3 PUFA-arme westliche Ernährung in Form von Kapseln ergänzen. Da diese Präparate beträchtlichen Variationen des Gehalts an langkettigen ω-3 PUFAs unterworfen sein können, haben wir neun kommerziell erhältliche Produkte bezugnehmend auf ihre Fettsäurekomposition getestet. METHODEN: Neun kommerziell erhältliche ω-3 PUFA Nahrungsergänzungsmittel wurden mittels kapillärer Gaschromatographie auf ihren Gehalt an langkettigen ω-3 PUFA untersucht. ERGEBNISSE: Die neun von uns getesteten Präparate zeigen hinsichtlich der Konzentration an langkettigen ω-3 PUFA große Unterschiede von bis zu 63,7 ± 1,58 mol % (p = 0,002) und die Meisten scheitern daran, die empfohlene Tagesdosis von einem Gramm zu erzielen, selbst wenn sie in der höchsten vom Hersteller angegebenen Dosierung verabreicht werden. Acht der Präparate enthalten entweder gleiche oder signifikant höhere langkettige ω-3 PUFA Mengen als vom Hersteller angegeben und ein Hersteller macht keine Angabe. Die höchsten Anteile an Eicosapentaensäure (EPA) und Docosahexaensäure (DHA) wurden in Omacor® (95,80 ± 0,63%) und Percucor® (76,8 ± 7,11%) vorgefunden. KONKLUSION: Verabreichung von langkettigen ω-3 Fettsäurepräparaten kann in großen Unterschieden der tatsächlich konsumierten Menge resultieren. Daher ist es empfehlenswert, die am höchsten standardisierten und gereinigten Produkte zu verwenden.SummaryBACKGROUND: Omega-3 polyunsaturated fatty acids (long-chain ω-3 PUFA) have proved to be beneficial in atherosclerosis, arrhythmia and hypertriglyceridemia in several studies, which has led national and international societies to recommend an intake of 1 g/d long-chain ω-3 PUFA for antiatherosclerotic and antiarrhythmic purposes or 2–4 g/d for a lipid lowering effect. Numerous preparations are marketed for supplementing western diet, which is low in long-chain ω-3 PUFA. Since these preparations vary in their long-chain ω-3 PUFA content, we tested nine commercially available products for their fatty acid composition. METHODS: Nine commercially available ω-3 fatty acid supplements were analyzed using capillary gas chromatography to determine their fatty acid content. RESULTS: The nine preparations showed huge differences, up to 63.7 ± 1.58 mol% (P = 0.002), in their longchain ω-3 fatty acid content. Most of them failed to achieve the daily recommended dose of 1 g, even when administered at the highest dosage according to the manufacturers recommendations. Eight of the preparations contained either equal or significantly greater amounts of long-chain ω-3 PUFA than denoted by the manufacturer; one preparation did not provide any information. The highest percentage of DHA and EPA was detected in Omacor® (95.80 ± 0.63%) and Percucor® (76.8 ± 7.109%). CONCLUSION: Administering long-chain ω-3 fatty acid preparations may result in huge differences in terms of the actual amount ingested. It is therefore advisable to use the most standardized and purified products available.

Adiponectin receptor R1 is upregulated by valproic acid but not by topiramate in human hepatoma cell line, HepG2

Valproic acid (VPA) is an effective and widely used anticonvulsant, associated with metabolic adverse effects such as weight gain, hyperinsulinemia, hyperleptinemia and hypoadiponectinemia. The aim of this study was to evaluate the influence of VPA and topiramate (TPM) on adiponectin binding receptors, adipoR1 and adipoR2, in human liver cancer cells, HepG2. AdipoR1 but not adipoR2 gene expression was upregulated by VPA treatment. TPM did neither affect adipoR1 nor adipoR2 gene expression. Given the tight association between VPA treatment, metabolic side effects and the adipocytokine-axis, upregulation of adipoR1 possibly represents a favoured and insulin-sensitizing mechanism.

Resistin impairs basal and insulin-induced glycogen synthesis by different mechanisms.

In the present study, we investigated the mechanisms by which resistin (100 nM, 1 h) affects glycogen synthesis in L6 skeletal muscle cells. The activity of glycogen synthase, the major enzyme in glycogen synthesis, is determined by both its covalent phosphorylation and allostery through intracellular glucose-6-phosphate. Covalent phosphorylation of glycogen synthase was not altered by resistin and, accordingly, phosphorylation of GSK-3alpha/beta and Akt remained unchanged. The rate of glucose-6-phosphate formation, however, was decreased by resistin both in the absence and presence of insulin; in the absence of insulin, resistin decreased glucose-6-phosphate formation by reducing hexokinase type I activity without affecting glucose uptake; by contrast, in the presence of insulin, resistin decreased glucose-6-phosphate formation by reducing the Vmax of glucose uptake without changing hexokinase type I activity. In conclusion, short-term resistin incubation impairs glycogen synthesis by reducing the rate of glucose-6-phosphate formation involving, however, differential mechanisms in basal and insulin-stimulated states.

Postprandial triglyceride-rich lipoproteins induce hepatic insulin resistance in HepG2 cells independently of their receptor-mediated cellular uptake

Highlights ► The pathophysiological link between NAFLD and hepatic insulin resistance is unknown. ► We studied the effect of postprandial lipoproteins on hepatic insulin sensitivity. ► Postprandial lipoproteins cause liver steatosis and hepatic insulin resistance. ► We characterize the underlying molecular mechanisms. ► Postprandial lipoproteins are a link between NAFLD and hepatic insulin resistance.