Bioorthogonal Imaging Uncovers Sex- and Diet-dependent Lipid Metabolic Changes in Drosophila Brain during Aging

Abstract Lipid metabolism has been associated with brain aging and is regulated by diet, however, the underlying mechanisms are elusive. Using deuterium water (D2O) probed stimulated Raman scattering (SRS) imaging, we demonstrated brain lipid metabolism in Drosophila manipulated by diet in an age- and sex-dependent manner, and important roles of glial insulin/IGF-1 signaling (IIS) pathway in brain lipid metabolism. High sugar diets enhanced lipogenesis while dietary restriction promotes both lipogenesis and lipolysis, and these effects were impaired in both chico1/+ and dfoxo Drosophila loss-of-function mutants. Lipid synthesis and mobilization in brain lipid droplets were reduced with aging, but old chico1/+ flies maintained high lipid metabolic activities whereas aged dfoxo mutants showed increased lipogenesis in females but decreased lipogenesis in males. Diet-regulated brain lipid metabolism did not show sexual difference in both mutants as that in control. Our study supports the crucial role of glial IIS in regulating brain lipid metabolism.