期刊
EXPERIMENTAL CELL RESEARCH
卷 315, 期 3, 页码 411-418出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2008.10.036
关键词
Preadipocyte; Adipogenesis; Macrophage; Inflammation; Rb; Cell cycle
资金
- Canadian Institutes of Health Research [MOP-43850]
- Heart and Stroke Foundation of Ontario Master's Studentships
This study examines the mechanisms underlying the anti-adipogenic effect of macrophage-secreted products. 3T3-L1 preadipocytes were induced to differentiate over 8 days in medium conditioned by murine J774 macrophages (MacCM). The inhibitory effect on lipid accumulation and expression of adipogenic markers was diminished when addition of MacCM was delayed to day 2 of differentiation. Clonal expansion, an early event required for 3T3-L1 adipogenesis, was reduced in the presence of MacCM (89%; n=3; p<0.001), and BrdU incorporation was impaired by 55% (n=3; p<0.01). Activation of ERK1/2 was not affected by MacCM, and neither was the expression of p27(kip1), a cyclin-dependent kinase inhibitor. However, phosphorylation of the retinoblastoma protein (Rb), required for cell cycle progression, was impaired by MacCM (94% inhibition; n=3; p<0.01). Differentiation-dependent expression, nuclear localization, and DNA binding ability of C/EBP beta were not inhibited by MacCM. Alterations in cell cycle-associated proteins may be important with respect to the anti-adipogenic action of MacCM. (C) 2008 Elsevier Inc. All rights reserved.
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