title: Adipokines identified as new downstream targets for adiponectin: lessons from adiponectin-overexpressing or -deficient mice.
abstract: Adipokines play a central role in the pathogenesis of the metabolic syndrome. Among them, adiponectin (ApN), a master regulator of immune and fuel homeostasis, is decreased. Identifying downstream adipokines targeted by ApN may help in deciphering this syndrome. We have generated transgenic mice, allowing persistent and moderate overexpression of ApN (ApN-Overex) specifically in white adipose tissue (AT). We took advantage of this model to unravel the adipokine secretion profile triggered by ApN. AT was fractionated into adipocytes and stromal-vascular cells (SVC), which were cultured for 8 h. Profiling of secretory products by antibody arrays and subsequent ELISAs showed that the secretion of three proinflammatory factors (IL-17B, IL-21, TNFα) and three hematopoietic growth factors [GF; thrombopoietin and granulocyte (macrophage) colony-stimulating-factors] was reduced in adipocytes of ApN-Overex mice compared with wild-type mice. In the SVC of these mice, besides the hematopoietic GFs, the secretion of another GF (vascular endothelial GF receptor 1), two chemokines (RANTES and ICAM-1), and two proinflammatory factors (IL-6 and IL-12p70) was reduced as well. Only one cytokine, IL-1 receptor 4, was oversecreted by SVC of ApN-Overex mice, which may exhibit anti-inflammatory properties. Most of these changes in secretion were due to corresponding changes in mRNAs. A reverse profile of adipokine expression was observed in ApN-KO mice. In conclusion, ApN regulates in vivo the secretion of downstream adipokines, thereby inducing a shift of the immune balance in both adipocytes and SVC toward a less inflammatory phenotype. These downstream adipokines may be new therapeutic targets for the management of the metabolic syndrome.
authors.affiliation: Endocrinology and Metabolism Unit, Faculty of Medicine, University of Louvain, Avenue Hippocrate 55, Brussels, Belgium.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ge
authors.forename: Laurence
authors.initials: L
authors.lastname: Ryken
authors.forename: Laurence
authors.initials: L
authors.lastname: Noel
authors.forename: Eléonore
authors.initials: E
authors.lastname: Maury
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Brichard
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D052242:Adiponectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D048049:Extracellular Signal-Regulated MAP Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose