Time filter

Source Type

Habich C.,Paul Langerhans Group for Integrative Physiology | Sell H.,Paul Langerhans Group for Integrative Physiology
Hormone Molecular Biology and Clinical Investigation | Year: 2015

Adipose tissue expansion is associated with adipocyte dysfunction and increased inflammatory processes. In the obese state, adipose tissue is characterized by an impaired intracellular stress defense system and dysbalanced heat shock response. Several members of the heat shock protein (HSP) family have been identified as novel adipokines released upon cellular stress, which might be a molecular link from adipose tissue inflammation to the cardiovascular system. Therefore, this review aims at summarizing and discussing our recent knowledge on HSPs in relation to obesity and their potential links to cardiovascular disease. Of particular importance/interest are two members of the HSP family, HSP60 and heme oxygenase 1 (HO-1), which have been well described as adipokines, and studied in the context of obesity and cardiovascular disease. HSP60 is regarded as a novel molecular link between adipose tissue inflammation and obesity-associated insulin resistance. The role of HO-1 induction in the obese state is well-documented, but a causal relationship between increased HO-1 levels and obesity-associated metabolic diseases is still controversial. Both HSP60 and HO-1 are also forthcoming targets for the treatment of cardiovascular disease, and the current knowledge will also be discussed in this review. © 2015 by De Gruyter.

Van Herpen N.A.,Maastricht University | Sell H.,Paul Langerhans Group for Integrative Physiology | Eckel J.,Paul Langerhans Group for Integrative Physiology | Schrauwen P.,Maastricht University | Mensink R.P.,Maastricht University
Hormone and Metabolic Research | Year: 2013

Obesity and insulin resistance are associated with low-grade systemic inflammation, which is related to increased concentrations of plasma FFAs, glucose, or insulin. Prolonged fasting induces insulin resistance due to elevated plasma FFAs, but is not accompanied by hyperinsulinemia or hyperglycemia. This makes it possible to study effects of physiologically increased FFA concentrations on inflammatory markers, when insulin and glucose concentrations are not increased. In random order, 10 healthy young lean men (mean BMI: 22.8 kg/m2) were fasted or fed in energy balance for 60 h with a 2-week wash-out period. Subjects stayed in a respiration chamber during the 60-h periods. Blood samples were taken after 12, 36, and 60 h. Then, a hyperinsulinemic-euglycemic clamp was performed. Fasting decreased insulin sensitivity by 45% and increased FFA concentrations 5-fold. Fasting did not change concentrations of the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-8, or of hs-CRP. Effects on vascular endothelial growth factor (VEGF) - which may positively relate to insulin resistance, and on chemerin and leptin - adipokines related to obesity, and obesity-related pathologies, were also studied. At t=60 h, VEGF concentrations were significantly increased during the fasted period (p<0.05). At the same time point, chemerin (p<0.01) and leptin (p<0.01) were significantly decreased after fasting. For leptin, this decrease was also significant after 36 h (p<0.01). Adiponectin levels remained unchanged. In healthy young lean men, fasting-induced increases in FFAs leading to insulin resistance do not cause changes in concentrations of the inflammatory cytokines. VEGF concentrations increased and those of chemerin decreased. © Georg Thieme Verlag KG Stuttgart · New York.

Rohrborn D.,Paul Langerhans Group for Integrative Physiology | Eckel J.,Paul Langerhans Group for Integrative Physiology | Eckel J.,German Center for Diabetes Research | Sell H.,Paul Langerhans Group for Integrative Physiology
FEBS Letters | Year: 2014

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. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Gorgens S.W.,Paul Langerhans Group for Integrative Physiology | Eckardt K.,Paul Langerhans Group for Integrative Physiology | Elsen M.,Paul Langerhans Group for Integrative Physiology | Tennagels N.,Sanofi S.A. | And 2 more authors.
Biochemical Journal | Year: 2014

CHI3L1 (chitinase-3-like protein 1) 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. In the present study, we examined the regulation of CHI3L1 in primary human skeletal muscle cells. Moreover, we analysed potential autocrine effects of CHI3L1. We show that myotubes express CHI3L1 in a differentiation-dependent manner. Furthermore, proinflammatory cytokines up-regulate CHI3L1 expression (6-fold) and release (3-fold). Importantly, CHI3L1 treatment blocked TNFa (tumour necrosis factor a)-induced inflammation by inhibiting NF-?B (nuclear factor ?B) activation in skeletal muscle cells. We show that this effect is mediated via PAR2 (protease-activated receptor 2). In addition, CHI3L1 treatment diminished the TNFa-induced expression and secretion of IL (interleukin)-8, MCP1 (monocyte chemoattractant protein 1) and IL-6. In addition, impaired insulin action at the level of Akt and GSK3a/ß (glycogen synthase kinase 3a/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 TNFa-mediated inflammation and insulin resistance in human skeletal muscle cells, potentially involving an auto-and/or para-crine mechanism. © The Authors Journal compilation © 2014 Biochemical Society.

Romacho T.,Paul Langerhans Group for Integrative Physiology | Elsen M.,Paul Langerhans Group for Integrative Physiology | Rohrborn D.,Paul Langerhans Group for Integrative Physiology | Eckel J.,Paul Langerhans Group for Integrative Physiology | Eckel J.,German Center for Diabetes Research
Acta Physiologica | Year: 2014

The discovery of adipokines has revealed adipose tissue as a central node in the interorgan 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, such as 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. 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. 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. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Discover hidden collaborations