Role of the Toll-like receptor 4/NF-κB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages

Takayoshi Suganami, Kanami Tanimoto-Koyama, Junko Nishida, Michiko Itoh, Xunmei Yuan, Shinji Mizuarai, Hidehito Kotani, Shoji Yamaoka, Kensuke Miyake, Seiichiro Aoe, Yasutomi Kamei, Yoshihiro Ogawa

Research output: Contribution to journalArticle

526 Citations (Scopus)

Abstract

OBJECTIVE - Previous studies demonstrated that obese adipose tissue is characterized by increased infiltration of macrophages, suggesting that they might represent an important source of inflammation. Using an in vitro coculture system composed of 3T3-L1 adipocytes and RAW264 macrophages, we previously demonstrated that saturated fatty acids (FAs) and tumor necrosis factor (TNF)-α derived from adipocytes and macrophages, respectively, play a major role in the coculture-induced inflammatory changes. METHODS AND RESULTS - Coculture of adipocytes and macrophages resulted in the activation of nuclear factor-κB (NF-κB), a primary regulator of inflammatory responses, in both cell types. Pharmacological inhibition of NF-κB markedly suppressed the coculture-induced production of proinflammatory cytokines and adipocyte lipolysis. Peritoneal macrophages obtained from Toll-like receptor 4 (TLR4) mutant mice exhibited marked attenuation of TNFα production in response to saturated FAs. Notably, coculture of hypertrophied adipocytes and TLR4-mutant macrophages resulted in marked inhibition of proinflammatory cytokine production and adipocyte lipolysis. We also observed that endogenous FAs, which are released from adipocytes via the β3-adrenergic stimulation, resulted in the activation of the TLR4/NF-κB pathway. CONCLUSION - These findings suggest that saturated FAs, which are released in large quantities from hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for TLR4, thereby inducing the inflammatory changes in both adipocytes and macrophages through NF-κB activation.

Original languageEnglish
Pages (from-to)84-91
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume27
Issue number1
DOIs
Publication statusPublished - Jan 1 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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