Timing of feeding mitigates metabolic effects of circadian disruption

Disrupted light-dark cycles and mistimed feeding are recognized metabolic stressors. In this study, we investigated the independent and combined effects of a 12:12 light:dark cycle, advanced by 6 h every 6 days (Chronic Disruption; CD), and time-restricted feeding on the metabolic health of male C57BL/6J mice. Ad libitum mice under the CD cycle gained significantly more body weight and body fat compared to animals under a control light cycle (LD), despite similar caloric intake and wheel running activity. Using specialized equipment to dissociate light cues from nutrient access, we demonstrate that light-cycle disruption induces metabolic dysfunction specifically through fragmented and misaligned eating patterns. Crucially, restricting food access to a 12-h window synchronized with the shifting dark phase abrogated the weight gain and adiposity observed in the ad libitum group. Conversely, shifting the feeding window under a stable light cycle significantly reduced food intake and weight gain, revealing that feeding regularity is a primary determinant of energy balance independent of light-cycle stability. Overall, while the light-dark cycle is the dominant zeitgeber for activity, the temporal consolidation of food intake is the primary driver of metabolic alignment, offering a potential intervention for managing metabolic risk in shift workers.