A lipid-binding protein that boosts daytime wake is mainly located at the body surface and blocks light-induced lipid...

We report a previously unrecognized brain vulnerability from visible-light exposure that is exacerbated by high-fat diets (HFDs). Prior work in Drosophila identified daywake (dyw), a predicted lipid/hormone-binding protein that stimulates wakefulness only when animals are exposed to visible light. Herein, we show that HFDs preferentially increase daytime sleep in dyw-null flies compared with wild-type flies, consistent with dyw's strong inducibility by HFD. This increased daytime sleep is causally linked to light-dependent reactive oxygen species (ROS) accumulation and lipid peroxidation at the blood-brain barrier (BBB) and cortex region of the brain, events which are eliminated by a return to darkness or dietary supplements with antioxidants. Although DYW is not detected in the brain, it is produced in thousands of sensory neurons at or near the body surface where it also blocks light-dependent lipid peroxidation. Our studies implicate the BBB as a key redox sensor linking peripheral oxidative stress to wake-sleep control. The potential toxicity from elevated brain ROS production due to increased neuronal activity during wakefulness is thought to be mainly cleared during nighttime sleep. We propose an additional adaptation for day-active life forms whereby antioxidant activity at the body surface limits the risk of visible-light exposure from triggering systemic increases in the levels of ROS and lipid peroxidation, thus lowering overall oxidative burden in the brain and, hence, the ability of visible light to safely stimulate enhanced wakefulness states.