title: Adipocyte-secreted chemerin is processed to a variety of isoforms and influences MMP3 and chemokine secretion through an NFkB-dependent mechanism.
abstract: Obesity is associated with white adipose tissue (WAT) remodelling characterized by changes in cellular composition, size, and adipokine secretion. Levels of the adipokine chemerin are positively associated with obesity; however, the biological function of chemerin in WAT is poorly understood. We identified factors involved in WAT remodelling, including matrix metalloproteinase (Mmp)3 and chemokines (Ccl2, 3, 5, 7), as novel targets of chemerin signalling in mature adipocytes. Inhibition of chemerin signalling increased MMP activity and the recruitment of macrophages towards adipocyte-conditioned media. These effects were mediated through increases in NFkB signalling, suggesting that chemerin exerts an anti-inflammatory influence. We also demonstrate that multiple chemerin isoforms are present in adipocyte-conditioned media and that adipocyte-secreted chemerin, but not synthetic chemerin, recapitulates the activity of endogenous chemerin. Considered altogether, this suggests that endogenously secreted chemerin plays an autocrine/paracrine role in WAT, identifying chemerin as a therapeutic target to modulate adipose remodelling.
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 4R2, Canada.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Dranse
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 4R2, Canada.
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Muruganandan
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 4R2, Canada; Department of Surgery, Dalhousie University, Halifax, NS, B3H 4R2, Canada.
authors.forename: James P
authors.initials: JP
authors.lastname: Fawcett
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, NS, B3H 4R2, Canada. Electronic address: csinal@dal.ca.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sinal
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018925:Chemokines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009500:Neutralization Tests; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D018925:Chemokines; D017077:Culture Media, Conditioned; C000591279:GPR1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D020033:Protein Isoforms; C478630:RARRES2 protein, human; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C523686:chemerin protein, mouse; D019278:Matrix Metalloproteinase 3
keywords: Adipocyte; Adipokine; Adipose remodelling; Chemerin; Inflammation; NFkB