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Adipocyte-secreted chemerin is processed to a variety of isoforms and influences MMP3 and chemokine secretion through an NFkB-dependent mechanism
- Dranse, Helen J., Muruganandan, Shanmugam, Fawcett, James P., Sinal, Christopher J.
- Molecular and Cellular Endocrinology 2016 v.436 pp. 114-129
- adipocytes, adipokines, autocrine signaling, chemokines, macrophages, metalloproteinases, obesity, secretion, white adipose tissue
- 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.