Macrophage-derived upd3 cytokine causes impaired glucose homeostasis and reduced lifespan in Drosophila fed a lipid-rich diet.
Immunity
; 42(1): 133-44, 2015 Jan 20.
Article
en En
| MEDLINE
| ID: mdl-25601202
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Envejecimiento Prematuro
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Proteínas de Drosophila
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Drosophila
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Macrófagos
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Obesidad
Tipo de estudio:
Etiology_studies
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Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article