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

Xiaoqian Hu, Vincenza Cifarelli, Shishuo Sun, Ondrej Kuda, Nada A. Abumrad, Xiong Su

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)663-673
Number of pages11
JournalJournal of lipid research
Volume57
Issue number4
DOIs
StatePublished - Apr 2016

Keywords

  • Adipose tissue
  • Cyclooxygenase
  • Eicosanoids
  • Extracellular signal-regulated kinase
  • Fatty acid
  • Inflammation
  • Lipase

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