期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 339, 期 1-2, 页码 105-113出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2011.04.004
关键词
Inflammation; Fat cells; Macrophages; Apoptosis; Insulin resistance
资金
- German Research Association [WA1096/3-2]
- Centre of Excellence Baden-Wuerttemberg Metabolic Disorders
- Baden-Wuerttemberg Ministry of Science, Research and Arts
- European Social Fund
- Ulm University
Obesity-associated macrophage infiltration into adipose tissue is responsible for both local and systemic inflammation. Recent findings suggest fat cell apoptosis as an initiator of macrophage recruitment. Here, we investigated the effects of an inflammatory micro-environment on fat cells using human THP-1 macrophages and SGBS adipocytes. Macrophage-secreted factors induced insulin resistance, inhibited insulin-stimulated Akt phosphorylation, and induced apoptosis of adipocytes. The apoptosis-inducing effect was even more pronounced in direct co-cultures of adipocytes and macrophages. Our data suggest a link between insulin resistance and apoptosis sensitivity. Accordingly, pharmacological and genetic inhibition of insulin signaling at the level of Akt2 sensitized adipocytes to apoptosis induction by macrophage-secreted factors. In conclusion, we describe here a novel interaction of macrophages and fat cells, i.e. induction of apoptosis. Our data suggest a feed-forward cycle in which macrophages further drive the inflammatory process by inducing insulin resistance and concomitant apoptosis of adipocytes. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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