J Eckel

German Diabetes Center, Düsseldorf, North Rhine-Westphalia, Germany

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Publications (220)739.29 Total impact

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    ABSTRACT: Nutritional factors such as casein hydrolysates and long chain polyunsaturated fatty acids have been proposed to exert beneficial metabolic effects. We aimed to investigate how a casein hydrolysate (eCH) and long chain polyunsaturated fatty acids could affect human primary adipocyte function in vitro. Incubation conditions with the different nutritional factors were validated by assessing cell vitality with lactate dehydrogenase (LDH) release and neutral red incorporation. Intracellular triglyceride content was assessed with Oil Red O staining. The effect of eCH, a non-peptidic amino acid mixture (AA), and long-chain polyunsaturated fatty acids (LC-PUFAs) on adiponectin and leptin secretion was determined by enzyme-linked immunosorbent assay (ELISA). Intracellular adiponectin expression and nuclear factor-κB (NF-κB) activation were analyzed by Western blot, while monocyte chemoattractant protein-1 (MCP-1) release was explored by ELISA. The eCH concentration dependently increased adiponectin secretion in human primary adipocytes through its intrinsic peptide bioactivity, since the non-peptidic mixture, AA, could not mimic eCH's effects on adiponectin secretion. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and DHA combined with arachidonic acid (ARA) upregulated adiponectin secretion. However, only DHA and DHA/ARA exerted a potentanti-inflammatory effect reflected by prevention of tumor necrosis factor-α (TNF-α) induced NF-κB activation and MCP-1 secretion in human adipocytes. eCH and DHA alone or in combination with ARA, may hold the key for nutritional programming through their anti-inflammatory action to prevent diseases with low-grade chronic inflammation such as obesity or diabetes.
    Nutrients 01/2015; 7(2):865-86. DOI:10.3390/nu7020865 · 3.15 Impact Factor
  • Diana Röhrborn, Jürgen Eckel, Henrike Sell
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    ABSTRACT: Dipeptidyl peptidase 4 is an important drug target for diabetes and a novel adipokine. However, it is unknown how soluble DPP4 (sDPP4) is cleaved from the cell membrane and released into the circulation. We show here that MMP1, MMP2 and MMP14 are involved in DPP4 shedding from human vascular smooth muscle cells (SMC) and MMP9 from adipocytes. Hypoxia increased DPP4 shedding from SMC which is associated with increased mRNA expression of MMP1. Our data suggest that constitutive as well as hypoxia-induced DPP4 shedding occurs due to a complex interplay between different MMPs in cell type-specific manner.
    FEBS Letters 09/2014; 588(21):3870-7. DOI:10.1016/j.febslet.2014.08.029 · 3.34 Impact Factor
  • Diabetes 09/2014; 63(9):e16. DOI:10.2337/db14-0776 · 7.90 Impact Factor
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    ABSTRACT: Adenosine monophosphate-activated protein kinase (AMPK) has been identified as one of the major targets for antidiabetic drugs. This study describes two AMPK-activating agents 2-(benzo[d]thiazol-2-ylmethylthio)-6-ethoxybenzo[d]thiazole and 2-(propylthio)benzo[d]thiazol-6-ol, that increase the rate of glucose uptake in L6 myotubes and also augment glucose-stimulated insulin secretion in INS-1E β-cells and rat islets. We believe that such unique bi-functional compounds can be further used for the development of a new class of antidiabetic drugs.
    Chemical Communications 08/2014; 50(76). DOI:10.1039/c4cc03310h · 6.38 Impact Factor
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    ABSTRACT: The health-promoting effects of regular exercise are well known, and myokines may mediate some of these effects. The small leucine-rich proteoglycan decorin has been described as a myokine for some time. However, its regulation and impact on skeletal muscle has not been investigated in detail. In this study, we report decorin to be differentially expressed and released in response to muscle contraction using different approaches. Decorin is released from contracting human myotubes, and circulating decorin levels are increased in response to acute resistance exercise in humans. Moreover, decorin expression in skeletal muscle is increased in humans and mice after chronic training. Because decorin directly binds myostatin, a potent inhibitor of muscle growth, we investigated a potential function of decorin in the regulation of skeletal muscle growth. In vivo overexpression of decorin in murine skeletal muscle promoted expression of the pro-myogenic factor Mighty, which is negatively regulated by myostatin. We also found Myod1 and follistatin to be increased in response to decorin overexpression. Moreover, muscle-specific ubiquitin ligases atrogin1 and MuRF1, which are involved in atrophic pathways, were reduced by decorin overexpression. In summary, our findings suggest that decorin secreted from myotubes in response to exercise is involved in the regulation of muscle hypertrophy and hence could play a role in exercise-related restructuring processes of skeletal muscle.
    Biochemical and Biophysical Research Communications 07/2014; 450(2). DOI:10.1016/j.bbrc.2014.06.123 · 2.28 Impact Factor
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    ABSTRACT: DPP4 is an ubiquitously expressed cell-surface protease that is shedded to the circulation as soluble DPP4 (sDPP4). We recently identified sDPP4 as a novel adipokine potentially linking obesity to the metabolic syndrome. The aim of this study was to investigate direct effects of sDPP4 on human vascular smooth muscle cells (hVSMC) and to identify responsible signaling pathways. Using physiological concentrations of sDPP4, we could observe a concentration-dependent activation of ERK1/2 (3-fold) after 6h, which remained stable for up to 24h. Additionally, sDPP4 treatment induced a 1.5-fold phosphorylation of the NF-κB subunit p65. In accordance with sDPP4-induced stress and inflammatory signaling, sDPP4 also stimulates hVSMC proliferation. Furthermore we could observe an increased expression and secretion of pro-inflammatory cytokines like interleukin (IL)-6, IL-8 and MCP-1 (2.5-, 2.4- and 1.5-fold, respectively) by the sDPP4 treatment. All direct effects of sDPP4 on signaling, proliferation and inflammation could completely be prevented by DPP4 inhibition. Bioinformatic analysis and signaling signature induced by sDPP4 suggest that sDPP4 might be an agonist for PAR2. After silencing of PAR2, the sDPP4-induced ERK activation as well as the proliferation was totally abolished. Additionally, the sDPP4-induced upregulation of IL-6 and IL-8 could completely be prevented by the PAR2 silencing. In conclusion, we show for the first time that sDPP4 directly activates the MAPK and NF-κB signaling cascade involving PAR2 and resulting in the induction of inflammation and proliferation of hVSMC. Thus, our in vitro data might extend the current view of sDPP4 action and shed light on cardiovascular effects of DPP4-inhibitors.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 06/2014; DOI:10.1016/j.bbadis.2014.06.004 · 5.09 Impact Factor
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    ABSTRACT: The 12th Stock Conference addressed body composition and related functions in two extreme situations, obesity and cancer cachexia. The concept of ‘functional body composition’ integrates body components into regulatory systems relating the mass of organs and tissues to corresponding in vivo functions and metabolic processes. This concept adds to an understanding of organ/tissue mass and function in the context of metabolic adaptations to weight change and disease. During weight gain and loss, there are associated changes in individual body components while the relationships between organ and tissue mass are fixed. Thus an understanding of body weight regulation involves an examination of the relationships between organs and tissues rather than individual organ and tissue masses only. The between organ/tissue mass relationships are associated with and explained by crosstalks between organs and tissues mediated by cytokines, hormones and metabolites that are coupled with changes in body weight, composition and function as observed in obesity and cancer cachexia. In addition to established roles in intermediary metabolism, cell function and inflammation, organ-tissue crosstalk mediators are determinants of body composition and its change with weight gain and loss. The 12th Stock Conference supported Michael Stocks' concept of gaining new insights by integrating research ideas from obesity and cancer cachexia. The conference presentations provide an in-depth understanding of body composition and metabolism.
    Obesity Reviews 06/2014; 15(8). DOI:10.1111/obr.12187 · 7.86 Impact Factor
  • Manuela Elsen, Silja Raschke, Juergen Eckel
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    ABSTRACT: The discovery of irisin as an exercise-regulated myokine inducing browning of WAT has attracted a lot of interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes. However, there are inconsistencies regarding the relevance of irisin in humans. The regulation of FNDC5 mRNA expression by exercise and contraction could not be reproduced by a number of human studies using several exercise protocols and in vitro approaches. Furthermore, the nature of FNDC5 fragments and the presence of irisin in humans are questionable and probably contribute to conflicting data obtained with commercially available ELISA kits. Most importantly, the concentration of circulating irisin in humans is not clear, since different studies using different kits measure irisin levels in a wide range. Data about the role of irisin in states of human obesity and metabolic diseases are conflicting and in case changes of irisin levels have been observed, they were only moderate with 10 - 20 %. Independently of the presence and regulation of FNDC5/irisin in humans, the application of recombinant irisin could still represent a therapeutic strategy to fight obesity. However, the current data obtained in human cell models show, that FNDC5/irisin has no effect on browning of the major WAT depots in humans and is likely to selectively target a small subpopulation of adipocytes, located in classical BAT regions, such as the supraclavicular adipose tissue. Thus, other candidates, such as BMP7 or CNPs seem to me more prominent candidates as inducers of browning in humans.
    Journal of Endocrinology 04/2014; 222(1). DOI:10.1530/JOE-14-0189 · 3.59 Impact Factor
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    ABSTRACT: Skeletal muscle represents the largest organ of the body in non-obese individuals and is now considered to be an active endocrine organ releasing a host of so-called myokines. These myokines are part of a complex network that mediates communication between muscle, the liver, adipose tissue, the brain and other organs. Recent data suggest that myokines regulated by muscle contraction may play a key role in mediating the health-promoting effects of regular physical activity. Although hundreds of myokines have recently been described in proteomic studies, we currently have a rather limited knowledge of the specific role these myokines play in the prevention of insulin resistance, inflammation and associated metabolic dysfunction. Several myokines are known to have both local and endocrine functions, but in many cases the contribution of physical activity to the systemic level of these molecules remains as yet unexplored. Very recently, novel myokines such as irisin, which is thought to induce a white to brown shift in adipocytes, have gained considerable interest as potential therapeutic targets. In this review, we summarise the most recent findings on the role of myokines in the regulation of substrate metabolism and insulin sensitivity. We further explore the role of myokines in the regulation of inflammation and provide a critical assessment of irisin and other myokines regarding their potential as therapeutic targets.
    Diabetologia 03/2014; 57(6). DOI:10.1007/s00125-014-3224-x · 6.88 Impact Factor
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    ABSTRACT: CHI3L1 is a glycoprotein consisting of 383 amino acids with a molecular mass of 40 kDa, and its serum level is elevated in inflammatory diseases. Although CHI3L1 is described as a biomarker of inflammation, the function of this protein is not completely understood. Here, we examined the regulation of CHI3L1 in primary human skeletal muscle cells. Moreover, we analyzed potential autocrine effects of CHI3L1. We show that myotubes express CHI3L1 in a differentiation-dependent manner. Furthermore, pro-inflammatory cytokines up-regulate CHI3L1 expression (6-fold) and release (3-fold). Importantly, CHI3L1 treatment blocked tumor necrosis factor α (TNFα) -induced inflammation by inhibiting NF-κB activation in skeletal muscle cells. We show that this effect is mediated via protease activated receptor 2 (PAR2). In addition, CHI3L1 treatment diminished the TNFα-induced expression and secretion of IL-8, MCP1 and IL-6. Also, impaired insulin action at the level of Akt and glycogen synthase kinase (GSK) 3α/ß phosphorylation and insulin-stimulated glucose uptake was normalized by CHI3L1. In conclusion, the novel myokine CHI3L1 which is induced by pro-inflammatory cytokines can counteract TNFα-mediated inflammation and insulin resistance in human skeletal muscle cells, potentially involving an auto/paracrine mechanism.
    Biochemical Journal 02/2014; DOI:10.1042/BJ20131151 · 4.78 Impact Factor
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    ABSTRACT: The discovery of adipokines has revealed adipose tissue as a central node in the inter-organ crosstalk network, which mediates the regulation of multiple organs and tissues. Adipose tissue is a true endocrine organ that produces and secretes a wide range of mediators regulating adipose tissue function in an auto-/paracrine manner and important distant targets like the liver, skeletal muscle, the pancreas and the cardiovascular system. In metabolic disorders such as obesity, enlargement of adipocytes leads to adipose tissue dysfunction and a shift in the secretory profile with an increased release of pro-inflammatory adipokines. Adipose tissue dysfunction has a central role in the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Besides the well-acknowledged role of adipokines in metabolic diseases, and the increasing number of adipokines being discovered in the last years, the mechanisms underlying the release of many adipokines from adipose tissue remain largely unknown. In order to combat metabolic diseases, it is crucial to better understand how adipokines can modulate adipose tissue growth and function. Therefore, we will focus on adipokines with a prominent role in auto-/paracrine crosstalk within the adipose tissue such as RBP4, HO-1, WISP2, SFRPs and chemerin. In order to depict the endocrine crosstalk between adipose tissue with skeletal muscle, the cardiovascular system and the pancreas, we will report the main findings regarding the direct effects of adiponectin, leptin, DPP4 and visfatin on skeletal muscle insulin resistance, cardiovascular function and β-cell growth and function. This article is protected by copyright. All rights reserved.
    Acta Physiologica 02/2014; DOI:10.1111/apha.12246 · 4.25 Impact Factor
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    ABSTRACT: Cardiovascular complications are common in patients with type 2 diabetes. Adipokines have been implicated in the induction of proliferative and pro-atherogenic alterations in human vascular smooth muscle cells (hVSMC). Other reports demonstrated the importance of the miRNA cluster miR-143/145 in the regulation of VSMC homeostasis and insulin sensitivity. Here we investigated whether the detrimental effects of adipokines on hVSMC function could be ascribed to alterations in miR-143/145 expression. Exposure of hVSMC to conditioned media (CM) from primary human subcutaneous adipocytes increased the expression of smooth muscle α-actin (SMA), and the miR-143/145 cluster, but markedly impaired the insulin-mediated phosphorylation of Akt and its substrate endothelial nitric oxide synthase (eNOS). Furthermore, CM promoted the phosphorylation of SMAD2 and p38, which have both been linked to miR-143/145 induction. Accordingly, the induction of miR-143/145 as well as the inhibition of insulin-mediated Akt- and eNOS-phosphorylation was prevented when hVSMC were treated with pharmacological inhibitors for Alk-4/5/7 and p38 before the addition of CM. Transfection of hVSMC with precursor miR-143, but not with precursor miR-145, resulted in impaired insulin-mediated phosphorylation of Akt and eNOS. This inhibition of insulin signaling by CM and miR-143 is associated with a reduction in the expression of the oxysterol-binding protein-related protein 8 (ORP8). Finally, knock-down of ORP8 resulted in impaired insulin-mediated phosphorylation of Akt in hVSMC. Thus, the detrimental effects of adipocyte-derived conditioned media on insulin action in primary hVSMC can be ascribed to the Alk- and p38-dependent induction of miR-143 and subsequent downregulation of ORP8.
    Biochimica et Biophysica Acta 02/2014; 1842:275-283. DOI:10.1016/j.bbadis.2013.12.001 · 4.66 Impact Factor
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    ABSTRACT: Monocyte chemoattractant protein-induced protein 1 (MCPIP1) encoded by the ZC3H12a gene (also known as Regnase-1) is involved in the regulation of degradation of mRNA of inflammatory modulators and for processing of pre-miRNA. These functions depend on the presence of the PIN domain. Moreover, MCPIP1 was described as a negative regulator of NF-κB and AP-1 signaling pathways although mechanisms underlying such activity remain unknown. We aimed at determining the role of MCPIP1 in adipogenesis. Here, we present evidence that Mcpip1 transcription is transiently activated during 3T3-L1 transition from pre- to adipocytes. However Mcpip1 protein expression is also strongly decreased at day one after induction of adipogenesis. Knockdown of Mcpip1 results in an upregulation of C/EBPβ and PPARγ mRNAs, whereas overexpression of MCPIP1 reduces the level of both transcription factors and impairs adipogenesis. MCPIP1-dependend modulation of C/EBPβ and PPARγ levels results in a modulation of the expression of downstream controlled genes. In addition, decreased C/EBPβ, but not PPARγ, depends on the activity of the MCPIP1 PIN domain, which is responsible for RNase properties of this protein. Together, these data confirm that MCPIP1 is a key regulator of adipogenesis.
    Biochimica et Biophysica Acta 01/2014; DOI:10.1016/j.bbamcr.2014.01.001 · 4.66 Impact Factor
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 01/2014; · 5.09 Impact Factor
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    ABSTRACT: Adipose tissue (AT) was long perceived as a passive lipid storage depot but it is now considered as an endocrine organ that produces a large number of mediators that affect metabolism, inflammation and coagulation. In obesity, the increased size of adipocytes and chronic low-grade inflammation within AT alter its normal physiological function. AT dysfunction results in altered production and secretion of adipokines, which in turn affect several tissues, e.g. the liver, skeletal muscles and vasculature, in a para- or endocrine manner. Numerous circulating proinflammatory mediators involved in the development of cardiovascular disease (CVD) are directly released from adipocytes, thereby linking obesity to an increased cardiovascular risk. In the current chapter, we focus, on the one hand, on a small selection of novel adipokines with a potentially strong link to CVD: soluble dipeptidyl peptidase-4, visfatin and lipocalin-2. On the other hand, we summarize the most recent findings on the novel cardioprotective adipokines omentin and apelin. © 2014 S. Karger AG, Basel.
    Frontiers of hormone research 01/2014; 43:79-92. DOI:10.1159/000360560 · 1.24 Impact Factor
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    ABSTRACT: While white adipose tissue (AT) is an energy storage depot, brown AT is specialized in energy dissipation. Uncoupling protein 1 (UCP1)-expressing adipocytes with a different origin than classical brown adipocytes have been found in white AT. These "brite" (brown-in-white) adipocytes may represent a therapeutic target to counteract obesity. Bone morphogenetic proteins (BMPs) play a role in the regulation of adipogenesis. Based on studies with murine cells, BMP4 is assumed to induce stem cell commitment to the white adipocyte lineage, whereas BMP7 promotes brown adipogenesis. There is evidence for discrepancies between mouse and human AT. Therefore we compared the effect of BMP4 and BMP7 on white-to-brown transition in primary human adipose stem cells (hASCs) from subcutaneous AT. Long-term exposure of hASCs to recombinant BMP4 or BMP7 during differentiation increased adipogenesis, as determined by lipid accumulation and PPARγ expression. Not only BMP7, but also BMP4 increased UCP1 expression in hASCs and decreased expression of the white-specific marker TCF21. The ability of hASCs to induce UCP1 in response to BMP4 and BMP7 markedly differed between donors and could be related to the expression of the brite marker CD137. However, mitochondrial content and oxygen consumption was not increased in hASCs challenged with BMP4 and BMP7. In conclusion, we showed for the first time that BMP4 has similar effects on white-to-brown transition as BMP7 in our human cell model. Thus, the roles of BMP4 and BMP7 in adipogenesis cannot always be extrapolated from murine to human cell models.
    AJP Cell Physiology 11/2013; 306(5). DOI:10.1152/ajpcell.00290.2013 · 3.71 Impact Factor
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    ABSTRACT: OBJECTIVE To study expression of the recently-identified adipokine dipeptidyl peptidase-4 (DPP4) in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of patients with various BMIs and insulin sensitivities, as well as to assess circulating DPP4 in relation to obesity and insulin sensitivity.RESEARCH DESIGN AND METHODSDPP4 expression was measured in SAT and VAT from 196 subjects with a wide range of BMIs and insulin sensitivities. DPP4 release was measured ex vivo in paired biopsies from SAT and VAT as well as in vivo from SAT of lean and obese patients. Circulating DPP4 was measured in insulin-sensitive and insulin-resistant BMI-matched obese patients.RESULTSDPP4 expression was positively correlated with BMI in both SAT and VAT, with VAT consistently displaying higher expression than SAT. Ex vivo release of DPP4 from adipose tissue explants was higher in VAT than in SAT in both lean and obese patients, with obese patients displaying higher DPP4 release than lean controls. Net release of DPP4 from adipose tissue was also demonstrated in vivo with greater release in obese subjects than in lean subjects and in women than in men. Insulin-sensitive obese patients had significantly lower circulating DPP4 than did obesity-matched insulin-resistant patients. In this experiment, DPP4 positively correlated with the amount of VAT, adipocyte size, and adipose tissue inflammation.CONCLUSIONSDPP4, a novel adipokine, has a higher release from VAT that is particularly pronounced in obese and insulin-resistant patients. Our data suggest that DPP4 may be a marker for visceral obesity, insulin resistance, and the metabolic syndrome.
    Diabetes care 10/2013; 36(12). DOI:10.2337/dc13-0496 · 7.74 Impact Factor
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    ABSTRACT: Brown adipose tissue has gained interest as a potential target to treat obesity and metabolic diseases. Irisin is a newly identified hormone secreted from skeletal muscle enhancing browning of white fat cells, which improves systemic metabolism by increasing energy expenditure in mice. The discovery of irisin raised expectations of its therapeutic potential to treat metabolic diseases. However, the effect of irisin in humans is unclear. Analyses of genomic DNA, mRNA and expressed sequence tags revealed that FNDC5, the gene encoding the precursor of irisin, is present in rodents and most primates, but shows in humans a mutation in the conserved start codon ATG to ATA. HEK293 cells transfected with a human FNDC5 construct with ATA as start codon resulted in only 1% full-length protein compared to human FNDC5 with ATG. Additionally, in vitro contraction of primary human myotubes by electrical pulse stimulation induced a significant increase in PGC1α mRNA expression. However, FNDC5 mRNA level was not altered. FNDC5 mRNA expression in muscle biopsies from two different human exercise studies was not changed by endurance or strength training. Preadipocytes isolated from human subcutaneous adipose tissue exhibited differentiation to brite human adipocytes when incubated with bone morphogenetic protein (BMP) 7, but neither recombinant FNDC5 nor irisin were effective. In conclusion, our findings suggest that it is rather unlikely that the beneficial effect of irisin observed in mice can be translated to humans.
    PLoS ONE 09/2013; 8(9):e73680. DOI:10.1371/journal.pone.0073680 · 3.53 Impact Factor
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    ABSTRACT: The skeletal muscle is a metabolically active tissue that secretes various proteins. These so-called myokines have been proposed to affect muscle physiology and to exert systemic effects on other tissues and organs. Yet, changes in the secretory profile may participate in the pathophysiology of metabolic diseases. The present study aimed at characterizing the secretome of differentiated primary human skeletal muscle cells (hSkMC) derived from healthy, adult donors combining three different mass spectrometry based non-targeted approaches as well as one antibody based method. This led to the identification of 548 non-redundant proteins in conditioned media from hSkmc. For 501 proteins, significant mRNA expression could be demonstrated. Applying stringent consecutive filtering using SignalP, SecretomeP and ER_retention signals databases, 305 proteins were assigned as potential myokines of which 12 proteins containing a secretory signal peptide were not previously described. This comprehensive profiling study of the human skeletal muscle secretome expands our knowledge of the composition of the human myokinome and may contribute to our understanding of the role of myokines in multiple biological processes. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.
    Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics 08/2013; DOI:10.1016/j.bbapap.2013.08.004 · 3.19 Impact Factor
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    ABSTRACT: Adipose tissue secrets adipokines and fatty acids, which may contribute to obesity-associated vascular dysfunction and cardiovascular risk. This study investigated which factors are responsible for the synergistic effect of adipokine and oleic acid- (OA-) induced proliferation of human vascular smooth muscle cells (VSMC). Adipocyte-conditioned medium (CM) from human adipocytes induces proliferation of VSMC in correlation to its vascular endothelial growth factor (VEGF) content. CM increases VEGF-receptor (VEGF-R) 1 and 2 expression and VEGF secretion of VSMC, while OA only stimulates VEGF secretion. VEGF neutralization abrogates CM- and OA-induced proliferation and considerably reduces proliferation induced by CM and OA in combination. VEGF release is higher from visceral adipose tissue (VAT) of obese subjects compared to subcutaneous adipose tissue (SAT) and VAT from lean controls. Furthermore, VEGF release from VAT correlates with its proliferative effect. Perivascular adipose tissue (PAT) from type 2 diabetic patients releases significantly higher amounts of VEGF and induces stronger proliferation of VSMC as compared to SAT and SAT/PAT of nondiabetics. In conclusion, VEGF is mediating CM-induced proliferation of VSMC. As this adipokine is released in high amounts from VAT of obese patients and PAT of diabetic patients, VEGF might link adipose tissue inflammation to increased VSMC proliferation.
    Mediators of Inflammation 07/2013; 2013:982458. DOI:10.1155/2013/982458 · 2.42 Impact Factor

Publication Stats

4k Citations
739.29 Total Impact Points


  • 2005–2014
    • German Diabetes Center
      • • Paul-Langerhans-Group for Integrative Physiology
      • • Institute of Clinical Biochemistry and Pathobiochemistry
      Düsseldorf, North Rhine-Westphalia, Germany
  • 1998–2012
    • Heinrich-Heine-Universität Düsseldorf
      • • German Diabetes Center
      • • Institute of Biochemistry
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2004–2011
    • The University of the West Indies, Trinidad and Tobago
      • Faculty of Medical Sciences
      City of Port-of-Spain, City of Port of Spain, Trinidad and Tobago
  • 2010
    • University of Liverpool
      • Institute of Ageing & Chronic Disease
      Liverpool, ENG, United Kingdom
  • 2007
    • Leiden University Medical Centre
      • Department of Molecular Cell Biology
      Leiden, South Holland, Netherlands
  • 2000–2006
    • Hebrew University of Jerusalem
      • Department of Pharmacology
      Yerushalayim, Jerusalem, Israel
  • 2003
    • University of Greifswald
      Griefswald, Mecklenburg-Vorpommern, Germany
  • 1999–2001
    • Mansoura University
      • Department of Physiology
      Al Manşūrah, Muhafazat ad Daqahliyah, Egypt
  • 1995–2001
    • Institut für Diabetes Gerhardt Katsch
      Karlsburg, Mecklenburg-Vorpommern, Germany