Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment

0459242 - FGÚ 2017 RIV US eng J - Journal Article
Hu, XQ. - Cifarelli, V. - Sun, SS. - Kuda, Ondřej - Abumrad, N. A. - Su, X.
Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment.
Journal of Lipid Research. Roč. 57, č. 4 (2016), s. 663-673. ISSN 0022-2275. E-ISSN 1539-7262
R&D Projects: GA MŠMT(CZ) LH14040
Institutional support: RVO:67985823
Keywords : adipose tissue * cyclooxygenase * eicosanoids * extracellular signal-regulated kinase * fatty acid * inflammation * lipase
Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition
Impact factor: 4.810, year: 2016

Obesity induces accumulation of adipose tissue macrophages (ATMs), which contribute to both local and systemic inflammation and modulate insulin sensitivity. Adipocyte lipolysis during fasting and weight loss also leads to ATM accumulation, but without proinflammatory activation suggesting distinct mechanisms of ATM recruitment. We examined the possibility that specific lipid mediators with anti-inflammatory properties are released from adipocytes undergoing lipolysis to induce macrophage migration. In the present study, we showed that conditioned medium (CM) from adipocytes treated with forskolin to stimulate lipolysis can induce migration of RAW 264.7 macrophages. In addition to FFAs, lipolytic stimulation increased release of prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2), reflecting cytosolic phospholipase A2 α activation and enhanced cyclooxygenase (COX) 2 expression. Reconstituted medium with the anti-inflammatory PGE2 potently induced macrophage migration while different FFAs and PGD2 had modest effects. The ability of CM to induce macrophage migration was abolished by treating adipocytes with the COX2 inhibitor sc236 or by treating macrophages with the prostaglandin E receptor 4 antagonist AH23848. In fasted mice, macrophage accumulation in adipose tissue coincided with increases of PGE2 levels and COX1 expression. Collectively, our data show that adipocyte-originated PGE2 with inflammation suppressive properties plays a significant role in mediating ATM accumulation during lipolysis.
Permanent Link: http://hdl.handle.net/11104/0259476