Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet.
Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet.
复制标题
DOI：
10.1016/j.immuni.2014.12.023
复制
发表时间：
2015-01-20
期刊：
影响因子：
32.4
通讯作者：
Geissmann, Frederic
中科院分区：
文献类型：
--
作者：
Woodcock, Katie J.;Kierdorf, Katrin;Pouchelon, Clara A.;Vivancos, Valerie;Dionne, Marc S.;Geissmann, Frederic
长期食用高脂肪食物与肥胖、巨噬细胞活化和炎症、代谢失衡和寿命缩短有关。我们利用果蝇遗传学研究巨噬细胞的作用和控制其对饮食应激反应的途径。喂食富含脂质饮食的苍蝇表现出脂肪储存增加，JAK-STAT信号系统激活，胰岛素敏感性降低，高血糖症和寿命缩短。果蝇巨噬细胞产生JAK-STAT激活细胞因子upd 3，在清道夫受体（crq）和JNK依赖的方式。巨噬细胞的基因耗竭或upd 3的巨噬细胞特异性沉默降低了JAK-STAT的激活，挽救了果蝇的胰岛素敏感性和寿命，但没有减少脂肪储存。NF-κB信号传导对观察到的表型没有贡献。这些结果鉴定了巨噬细胞中进化上保守的“清道夫受体-JNK-1型细胞因子”盒，其通过激活JAK-STAT途径控制葡萄糖代谢并减少维持富含脂质饮食的果蝇的寿命。长期高脂饮食导致果蝇JAK-STAT激活长期JAK-STAT激活降低寿命和胰岛素敏感性高脂饮食诱导巨噬细胞产生JNK途径依赖性upd 3巨噬细胞upd 3控制JAK-STAT激活、存活和胰岛素敏感性在不同物种中，脂肪食物的消耗与炎症、代谢失衡和寿命缩短有关。Woodcock等人使用喂食富含脂质饮食的果蝇来证明巨噬细胞中进化上保守的“清道夫受体-JNK-1型细胞因子”盒通过激活JAK-STAT途径控制葡萄糖代谢并缩短寿命。
Long-term consumption of fatty foods is associated with obesity, macrophage activation and inflammation, metabolic imbalance, and a reduced lifespan. We took advantage of Drosophila genetics to investigate the role of macrophages and the pathway(s) that govern their response to dietary stress. Flies fed a lipid-rich diet presented with increased fat storage, systemic activation of JAK-STAT signaling, reduced insulin sensitivity, hyperglycemia, and a shorter lifespan. Drosophila macrophages produced the JAK-STAT-activating cytokine upd3, in a scavenger-receptor (crq) and JNK-dependent manner. Genetic depletion of macrophages or macrophage-specific silencing of upd3 decreased JAK-STAT activation and rescued insulin sensitivity and the lifespan of Drosophila, but did not decrease fat storage. NF-κB signaling made no contribution to the phenotype observed. These results identify an evolutionarily conserved “scavenger receptor-JNK-type 1 cytokine” cassette in macrophages, which controls glucose metabolism and reduces lifespan in Drosophila maintained on a lipid-rich diet via activation of the JAK-STAT pathway. Chronic lipid-rich diet results in JAK-STAT activation in Drosophila Chronic JAK-STAT activation reduces lifespan and insulin sensitivity Lipid-rich diet induces JNK pathway-dependent production of upd3 by macrophages Macrophage upd3 controls JAK-STAT activation, survival, and insulin sensitivity Consumption of fatty foods is associated across species with inflammation, metabolic imbalance, and reduced lifespan. Woodcock et al. use Drosophila fed a lipid-rich diet to demonstrate that an evolutionarily conserved “scavenger receptor-JNK-type 1 cytokine” cassette in macrophages controls glucose metabolism and reduces lifespan via activation of the JAK-STAT pathway.
登录
查看更多内容
影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
9.2
作者：
Clark, Rebecca I.;Woodcock, Katie J.;Geissmann, Frederic;Trouillet, Celine;Dionne, Marc S.
通讯作者：
Dionne, Marc S.
影响因子：
1.2
作者：
Bach, Erika A.;Ekas, Laura A.;Baeg, Gyeong-Hun
通讯作者：
Baeg, Gyeong-Hun
影响因子：
64.5
作者：
Hou, XS;Melnick, MB;Perrimon, N
通讯作者：
Perrimon, N
影响因子：
29
作者：
Birse RT;Choi J;Reardon K;Rodriguez J;Graham S;Diop S;Ocorr K;Bodmer R;Oldham S
通讯作者：
Oldham S