期刊
IMMUNITY
卷 42, 期 1, 页码 133-144出版社
CELL PRESS
DOI: 10.1016/j.immuni.2014.12.023
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资金
- DFG (German Research Foundation)
- Wellcome Trust [WT101853MA]
- ERC Investigator award from the European Research Council [2010-StG-261299]
- BBSRC [BB/L020122/1] Funding Source: UKRI
- MRC [MR/L018802/1, MR/L018802/2] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/L020122/1] Funding Source: researchfish
- Medical Research Council [MR/L018802/1, MR/L018802/2] Funding Source: researchfish
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-kappa B 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.
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