1. Adipocyte-secreted chemerin is processed to a variety of isoforms and influences MMP3 and chemokine secretion through an NFkB-dependent mechanism.
- Author
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Dranse HJ, Muruganandan S, Fawcett JP, and Sinal CJ
- Subjects
- Adipocytes drug effects, Amino Acid Sequence, Animals, Antibodies, Neutralizing pharmacology, Cell Differentiation drug effects, Chemokines chemistry, Chemokines genetics, Culture Media, Conditioned pharmacology, Humans, Intercellular Signaling Peptides and Proteins chemistry, Intercellular Signaling Peptides and Proteins genetics, Mass Spectrometry, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells drug effects, Mesenchymal Stem Cells metabolism, Mice, Inbred C57BL, Neutralization Tests, Protein Isoforms metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Chemokine genetics, Receptors, Chemokine metabolism, Receptors, G-Protein-Coupled metabolism, Signal Transduction drug effects, Up-Regulation drug effects, Adipocytes metabolism, Chemokines metabolism, Intercellular Signaling Peptides and Proteins metabolism, Matrix Metalloproteinase 3 metabolism, NF-kappa B metabolism, Protein Processing, Post-Translational drug effects
- 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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
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