Preadipocyte response and impairment of differentiation in an inflammatory environment.
Recent reports suggest the potential role of toll-like receptor 4 (TLR4) in initiation of inflammatory responses and fatty acid-induced insulin resistance. We describe here the synthesis of pro-inflammatory products in 3T3-L1 preadipocyte cell line after stimulation with lipopolysaccharide (LPS), a TLR4 agonist. Expression profiles of mRNA coding for IL6, CCL2, CCL5, CCL11, NOS2, and PTGS2 demonstrated a higher responsiveness to LPS of these transcripts in preadipocytes than in fully differentiated adipocytes, confirming inflammatory features of preadipocytes. IL6, CCL2, CCL5 and CCL11 were secreted in 3T3-L1 supernatants within 4 h after LPS stimulation. In addition, continuous exposure to LPS during adipocyte differentiation impaired this process as was demonstrated by analysis of mRNA profiles of lipogenesis enzymes (FABP4, GPD1, LPL), adipokines (adiponectin, resistin, visfatin, leptin), and of the transcription factor PPARgamma. This suggests that toll-like receptor mediated activation could regulate maintenance of preadipocyte status, and inflammatory environment encountered in inflamed white adipose tissue.
Poulain-Godefroy
Odile
O
CNRS 8090, Institute of Biology, Pasteur Institute, 1 rue Calmette, BP447, 59021 Lille, France. odile.poulain@good.ibl.fr
Froguel
Philippe
P
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D018925:Chemokines / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2