Study of the proinflammatory role of human differentiated omental adipocytes

Abstract

Infiltration of monocyte-derived macrophages into adipose tissue has been associated with tissue and systemic inflammation. It has been suggested that macrophage infiltration affects fat expansion through a paracrine action on adipocyte differentiation. Our working hypothesis is that factors released by monocytes/macrophages may also affect mature adipocyte biology. Human differentiated omental adipocytes were incubated with LPS and conditioned media obtained from human macrophage-like cell line THP-1, previously activated or not with LPS. We show that LPS greatly increased the secretion levels of pro-inflammatory adipokines including IL-6, IL-8, GRO, and MCP-1. Macrophage-conditioned medium also upregulated IL-6, IL-8, GRO, and MCP-1 mRNA expression and protein levels and led to the novo secretion of ICAM-1, IL-1β, IP-10, MIP-1α, MIP-1β, VEGF, and TNFα. Human differentiated adipocytes treated by macrophage-conditioned medium displayed marked reduction of adipocyte function as assessed by decreased phosphorylation levels of ERK1, ERK2, and p38α and reduced gene expression of lipogenic markers including PPAR-γ and fatty acid synthase. These data show that macrophage-secreted factors not only inhibit the formation of mature adipocytes but alter their function, suggesting that human differentiated omental adipocytes might also contribute to systemic chronic low-grade inflammation associated with human obesity. J. Cell. Biochem. 107: 1107–1117, 2009. © 2009 Wiley-Liss, Inc.