Study of the proinflammatory role of human differentiated omental adipocytes.
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-1 beta, IP-10, MIP-1 alpha, MIP-1 beta, VEGF, and TNFalpha. Human differentiated adipocytes treated by macrophage-conditioned medium displayed marked reduction of adipocyte function as assessed by decreased phosphorylation levels of ERK1, ERK2, and p38 alpha and reduced gene expression of lipogenic markers including PPAR-gamma 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.
Bassols
Judit
J
Department of Diabetes, Endocrinology and Nutrition, Hospital of Girona Dr. Josep Trueta, Biomedical Research Institute and CIBEROBN Fisiopatología de la Obesidad y Nutrición CB06/03/010, Girona, Spain.
Ortega
Francisco J
FJ
Moreno-Navarrete
José M
JM
Peral
Belén
B
Ricart
Wifredo
W
Fernández-Real
Jose-Manuel
JM
D017667:Adipocytes / Q000473:pathology*; D054392:Adipokines / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D009765:Obesity / Q000473:pathology; D009852:Omentum / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis
D054392:Adipokines; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger