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Human adipocyte‐derived triglyceride activates the unfolded protein response in THP‐1 macrophages
Author(s) -
Denton Jerod,
Fallen Katherine,
Ullery Jody,
Cox Brian,
Ueda Yukiko,
Banerjee Sreedatta,
Torquati Alfonso,
Abumrad Naji,
Jerome Jay
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a456-a
Subject(s) - adipocyte , adipose tissue , unfolded protein response , adipose tissue macrophages , lipid droplet , secretion , cytokine , microbiology and biotechnology , chemistry , macrophage , triglyceride , lipid metabolism , endocrinology , biology , medicine , cholesterol , biochemistry , immunology , endoplasmic reticulum , white adipose tissue , in vitro
Central obesity is associated with the infiltration of macrophages into adipose tissue. The function of macrophages in fat tissue is unknown; however recent studies suggest they may serve to scavenge free lipid from necrotic adipocytes. The uptake of lipids by some non‐adipose cells induces ER stress and activates the unfolded protein response (UPR). The UPR is coupled to signaling pathways known to induce inflammatory cytokine secretion in macrophages. Since these cytokines contribute to the development of metabolic syndrome, we tested the hypothesis that uptake of adipocyte lipid induces the UPR in macrophages. Triglyceride‐rich lipid dispersions (LD) were generated from lipid extracted from human omental adipose tissue of morbidly obese subjects and incubated with human THP‐1 macrophages in culture. Treatment of THP‐1 macrophages with LD led to a striking accumulation of neutral lipids, but only a nominal increase in total cellular cholesterol. Importantly, LD activated the UPR in these cells. The UPR was also activated by palmitate, which comprises 20% of acyl chains present in adipocyte lipids and LD. Our work suggests that scavenging adipocyte lipids may trigger signaling pathways that promote inflammatory cytokine secretion by macrophages. We are currently working to define the mechanisms by which lipids induce the UPR and test if this pathway is coupled to cytokine secretion in macrophages.