RNA sequencing data from the guts of Drosophila wildtype and CG3740/nazo double mutant 20-day-old males

Lipid dyshomeostasis has been implicated in a variety of diseases ranging
from obesity to neurodegenerative disorders such as Neurodegeneration with
Brain Iron Accumulation (NBIA). Here, we uncover the physiological role of
Nazo, the Drosophilamelanogaster homolog of the NBIA-mutated protein –
c19orf12, whose function has been elusive. Ablation of Drosophila c19orf12
homologs leads to dysregulation of multiple lipid metabolism genes. nazo
mutants exhibit markedly reduced gut lipid droplet and whole-body
triglyceride contents. Consequently, they are sensitive to starvation and
oxidative stress. Nazo is required for maintaining normal levels of
Perilipin-2, an inhibitor of the lipase – Brummer. Concurrent knockdown of
Brummer or overexpression of Perilipin-2 rescues the nazo phenotype,
suggesting that this defect, at least in part, may arise from diminished
Perilipin-2 on lipid droplets leading to aberrant Brummer-mediated
lipolysis. Our findings potentially provide novel insights into the role
of c19orf12 as a possible link between lipid dyshomeostasis and
neurodegeneration, particularly in the context of NBIA.