Oxidative Stress Promotes Eating Behavior and Obesity in C. elegans via EGL-4 / DAF-16 Signaling

Oxidative stress is associated with pathophysiological progress of many diseases. The objective of study was to investigate whether increased environmental oxidative stress stimulation can promote excessive eating behavior, a common cause of obesity, and to identify the molecular mechanism. The cGMP-dependent kinase (PKG) activator 8-pCPT-cGMP was applied in worm swimming assay to study behavior shifting between quiescence and foraging in C. elegans . Genetically modified C. elegans ( egl-4 loss or gain of function, and daf-16 mutant) were treated with paraquat, an oxidative stress inducer. Worm’s foraging behavior, body fat accumulation and body length were determined. The foxo1::gfp -transfected HEK293 cells and C. elegans ( daf-16 :: gfp TJ356) were further used to examine the effect of paraquat on PKG expression and FOXO nuclear translocation. A novel swimming assay using PKG activator stimulation was developed, which allows the rapid and effective study of foraging behavior in C. elegans . Paraquat treatment significantly inhibited quiescence, promoted foraging behavior, increased body fat accumulation and body growth. These responses were associated with diminished PKG expression/activation and increased FOXO (DAF-16) nuclear translocation in both transfected C. elegans and HEK293 cells. Our data suggest that PKG/FOXO signaling may plays an important role in mediating oxidative stress-induced excessive eating behavior and obesity development.