Gene expression profile of hemocytes from Drosophila melanogaster on lipid-enriched diet compared to normal 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 JAK-STAT activation, reduced insulin sensitivity and hyperglycaemia, and a shorter lifespan. Drosophila macrophages scavenged lipids and produced the type 1 cytokine upd3, in a scavenger-receptor (croquemort) 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 signalling 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 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 JAK-STAT activation, reduced insulin sensitivity and hyperglycaemia, and a shorter lifespan. Drosophila macrophages scavenged lipids and produced the type 1 cytokine upd3, in a scavenger-receptor (croquemort) 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 signalling 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

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE63254 | GEO | 2015/01/30

SECONDARY ACCESSION(S): PRJNA267110

REPOSITORIES: GEO