Division of Pediatric Endocrinology, Diabetes and Obesity Unit, Department of Pediatrics and Adolescent Medicine, Ulm University, Eythstr. 24, 89075 Ulm, Germany.
Mol Cell Endocrinol. 2011 Jun 6;339(1-2):105-13. doi: 10.1016/j.mce.2011.04.004. Epub 2011 Apr 9.
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.
肥胖相关的巨噬细胞浸润到脂肪组织中是引起局部和全身炎症的原因。最近的研究结果表明脂肪细胞凋亡是招募巨噬细胞的启动子。在这里，我们使用人源 THP-1 巨噬细胞和 SGBS 脂肪细胞研究了炎症微环境对脂肪细胞的影响。巨噬细胞分泌的因子诱导了胰岛素抵抗，抑制了胰岛素刺激的 Akt 磷酸化，并诱导了脂肪细胞凋亡。在脂肪细胞和巨噬细胞的直接共培养中，这种诱导凋亡的作用更为明显。我们的数据表明胰岛素抵抗和细胞凋亡敏感性之间存在联系。相应地，通过 Akt2 水平的胰岛素信号的药理学和遗传学抑制使脂肪细胞对巨噬细胞分泌因子诱导的细胞凋亡更为敏感。总之，我们在这里描述了巨噬细胞和脂肪细胞之间的一种新的相互作用，即诱导凋亡。我们的数据表明，这是一个正反馈循环，其中巨噬细胞通过诱导胰岛素抵抗和伴随的脂肪细胞凋亡来进一步推动炎症过程。
