Unknown

Dataset Information

0

Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet.


ABSTRACT: 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.

SUBMITTER: Woodcock KJ 

PROVIDER: S-EPMC4304720 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7286907 | biostudies-literature
| S-EPMC5906610 | biostudies-literature
| S-EPMC8302672 | biostudies-literature
| S-EPMC8282274 | biostudies-literature
| S-EPMC3948039 | biostudies-literature
| S-EPMC2737162 | biostudies-literature
| S-EPMC8282463 | biostudies-literature
| S-EPMC8456208 | biostudies-literature
| S-EPMC5690694 | biostudies-literature
| S-EPMC8139119 | biostudies-literature