Search Results
You are looking at 1 - 4 of 4 items for
- Author: Matthias Bluher x
- Refine by access: All content x
Search for other papers by Sebastian Weise in
Google Scholar
PubMed
Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany
Search for other papers by Susan Kralisch in
Google Scholar
PubMed
Search for other papers by Grit Sommer in
Google Scholar
PubMed
Search for other papers by Ulrike Lossner in
Google Scholar
PubMed
Search for other papers by Matthias Bluher in
Google Scholar
PubMed
Search for other papers by Michael Stumvoll in
Google Scholar
PubMed
Department of Internal Medicine III, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, University of Leipzig, 04103 Leipzig, Germany
Search for other papers by Mathias Fasshauer in
Google Scholar
PubMed
The adipokine tissue inhibitor of metalloproteinase (TIMP)-1 is upregulated when weight is gained and promotes adipose tissue development. In the present study, the effect of insulin resistance-inducing and proinflammatory interleukin (IL)-1β on TIMP-1 gene expression and secretion was investigated in 3T3-L1 adipocytes. Interestingly, protein secretion and mRNA production of TIMP-1 were significantly stimulated by IL-1β. Thus, IL-1β induced TIMP-1 secretion in a dose-dependent manner with maximal 3.5-fold upregulation seen at 0.67 ng/ml IL-1β relative to untreated cells. Furthermore, TIMP-1 mRNA synthesis was significantly stimulated by IL-1β in a dose-dependent fashion with 2.5-fold induction seen at IL-1β concentrations as low as 0.02 ng/ml and maximal 8.1-fold upregulation found at 20 ng/ml effector. Induction of TIMP-1 mRNA was also time dependent with maximal 9.6-fold upregulation detectable after 8 h of IL-1β treatment. Signaling studies suggested that janus kinase 2 is involved in IL-1β-induced TIMP-1 mRNA expression. Taken together, our results demonstrate that the TIMP-1 expression is selectively upregulated by proinflammatory IL-1β, supporting a direct association between insulin resistance, inflammation, and adipose tissue development in obesity.
Search for other papers by Mathias Fasshauer in
Google Scholar
PubMed
Search for other papers by Johannes Klein in
Google Scholar
PubMed
Search for other papers by Susan Kralisch in
Google Scholar
PubMed
Search for other papers by Margit Klier in
Google Scholar
PubMed
Search for other papers by Ulrike Lossner in
Google Scholar
PubMed
Search for other papers by Matthias Bluher in
Google Scholar
PubMed
Search for other papers by Ralf Paschke in
Google Scholar
PubMed
A chronic increase in systemic levels of acute-phase reactants contributes to the development of insulin resistance and associated disorders such as cardiovascular disease. Recently, serum amyloid A3 (SAA3) has been characterized as an adipocyte-secreted acute-phase reactant, expression of which is dramatically increased in insulin resistance and obesity. To further clarify expression and regulation of this adipocytokine in fat, SAA3 mRNA was measured by quantitative real-time reverse transcriptase PCR during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance and contribute to atherosclerosis. SAA3 mRNA was dramatically induced up to 77-fold during differentiation of 3T3-L1 preadipocytes. Furthermore, 100 nM dexamethasone and 30 ng/ml interleukin (IL)-6 induced SAA3 mRNA by up to 11- and 4.8-fold, respectively, in a time-dependent fashion with significant stimulation observed at concentrations as low as 10 nM dexamethasone and 1 ng/ml IL-6. In contrast, insulin, isoproterenol and growth hormone did not influence SAA3 synthesis. Inhibitor studies suggested that the positive effect of IL-6 on SAA3 expression is at least in part mediated by Janus kinase 2. Taken together, our results show a differential regulation of SAA3 by glucocorticoids and IL-6 supporting an integrative role of this acute-phase reactant in the pathogenesis of insulin resistance and its link to obesity and cardiovascular disease.
University of Lübeck, Department of Internal Medicine I, 23538 Lübeck, Germany
Search for other papers by Susan Kralisch in
Google Scholar
PubMed
University of Lübeck, Department of Internal Medicine I, 23538 Lübeck, Germany
Search for other papers by Johannes Klein in
Google Scholar
PubMed
University of Lübeck, Department of Internal Medicine I, 23538 Lübeck, Germany
Search for other papers by Ulrike Lossner in
Google Scholar
PubMed
University of Lübeck, Department of Internal Medicine I, 23538 Lübeck, Germany
Search for other papers by Matthias Bluher in
Google Scholar
PubMed
University of Lübeck, Department of Internal Medicine I, 23538 Lübeck, Germany
Search for other papers by Ralf Paschke in
Google Scholar
PubMed
University of Lübeck, Department of Internal Medicine I, 23538 Lübeck, Germany
Search for other papers by Michael Stumvoll in
Google Scholar
PubMed
University of Lübeck, Department of Internal Medicine I, 23538 Lübeck, Germany
Search for other papers by Mathias Fasshauer in
Google Scholar
PubMed
Recently, visfatin was characterized as a novel adipo-cytokine that is upregulated in obesity and exerts insulin-mimetic effects in various tissues. To clarify expression and regulation of this adipocytokine, visfatin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction in 3T3-L1 adipocytes during adipogenesis and after treatment with various hormones known to alter insulin sensitivity. Visfatin expression was about 6-fold higher in 3T3-L1 adipocytes in vitro as compared with epididymal fat in vivo and increased during adipogenic conversion more than 3-fold. Interestingly, 100 nM dexamethasone significantly increased visfatin mRNA by almost 1.5-fold. In contrast, 500 ng/ml growth hormone (GH), 10 ng/ml tumor necrosis factor (TNF) α, and 10 μM isoproterenol downregulated visfatin expression by 45%, 36%, and 43% respectively. Insulin did not influence synthesis of this adipocytokine. The effects of dexamethasone, GH, TNFα and isoproterenol were time- and dose-dependent. Furthermore, activation of Gs-protein-coupled pathways by forskolin and cholera toxin was sufficient to significantly downregulate visfatin mRNA. Taken together, our results show a differential regulation of visfatin mRNA by insulin resistance-inducing hormones, supporting the view that this adipo-cytokine might be an interesting novel candidate linking core components of the metabolic syndrome such as obesity and insulin resistance.
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Search for other papers by Susan Kralisch in
Google Scholar
PubMed
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Search for other papers by Anke Tönjes in
Google Scholar
PubMed
Search for other papers by Kerstin Krause in
Google Scholar
PubMed
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Search for other papers by Judit Richter in
Google Scholar
PubMed
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Search for other papers by Ulrike Lossner in
Google Scholar
PubMed
Search for other papers by Peter Kovacs in
Google Scholar
PubMed
Search for other papers by Thomas Ebert in
Google Scholar
PubMed
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Search for other papers by Matthias Blüher in
Google Scholar
PubMed
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Search for other papers by Michael Stumvoll in
Google Scholar
PubMed
Medical Department, Leipzig University Medical Center, LIFE Study Center, University of Leipzig, Liebigstrasse 18, 04103 Leipzig, Germany
Search for other papers by Mathias Fasshauer in
Google Scholar
PubMed
Rather than a traditional growth factor, fibroblast growth factor-21 (FGF21) is considered to be a metabolic hormone. In the current study, we investigated serum FGF21 levels in the self-contained population of Sorbs. Serum FGF21 concentrations were quantified by ELISA and correlated with IGF1 as well as metabolic, renal, hepatic, inflammatory, and cardiovascular parameters in 913 Sorbs from Germany. Moreover, human IGF1 protein secretion was investigated in FGF21-stimulated HepG2 cells. Median FGF21 serum concentrations were 2.1-fold higher in subjects with type 2 diabetes mellitus (141.8 ng/l) compared with controls (66.7 ng/l). Furthermore, nondiabetic subjects with FGF21 levels below the detection limit of the ELISA showed a more beneficial metabolic profile compared with subjects with measurable FGF21. Moreover, FGF21 was significantly lower in female compared with male subjects after adjustment for age and BMI. In multiple regression analyses, circulating FGF21 concentrations remained independently and positively associated with gender, systolic blood pressure, triglycerides, and γ glutamyl transferase whereas a negative association was observed with IGF1 in nondiabetic subjects. Notably, FGF21 significantly inhibited IGF1 secretion into HepG2 cell culture supernatants in preliminary in vitro experiments. FGF21 serum concentrations are associated with facets of the metabolic syndrome, hepatocellular function, as well as GH status.