Time-restricted feeding attenuates allergic dermatitis in mice and is associated with modulation of leptin-driven inflammatory pathways

Irregular and unhealthy eating behavior contributes to the development of both metabolic and inflammatory disorders. Time-restricted eating modulates metabolism and immune function without reducing caloric intake, yet its role in inflammatory skin diseases remains unclear. Here, we examined how feeding time and diet influence contact hypersensitivity, a murine model of allergic dermatitis--a disease that affects 20% of the population. Mice were fed with normal (NC) or high-fat (HF) chow under ad libitum (AL) or 10/14 time-restricted feeding (TRF) conditions. Under AL conditions, HF diet induced metabolic dysfunction and exacerbated inflammation, characterized by increased ear swelling, leukocyte infiltration, neutrophil and cytokine accumulation, and intraepidermal pustule formation. TRF attenuated these effects and accelerated resolution, even when initiated after disease onset. HF feeding altered both the level and diurnal dynamics of serum leptin, while TRF partially restored these changes. Elevated leptin levels were associated with increased inflammatory responses including intense neutrophil accumulation and pustule formation, and both genetic and pharmacological inhibition of leptin signaling reduced disease severity. Analysis of patients transcriptomic data also suggested a link between leptin signaling and inflammatory skin conditions in humans. We propose that time-restricted eating beneficially influences disease progression in contact dermatitis and that leptin-associated pathways may contribute to this effect.