Temporal control of feeding attenuates allergic dermatitis via reduced leptin production in mice

Limiting food access to a specific time window of the day, without caloric restriction, helps prevent and treat metabolic diseases. Given the close connection between metabolism and immune function, we investigated how meal timing affects acute and subacute forms of contact hypersensitivity (CHS) in mice on normal (NC) and high-fat (HF) diet. Under conditions with ad libitum (AL) food access, HF diet resulted in increased ear thickness, leukocyte infiltration, pustule formation, IL-1β, CXCL2 levels and markedly delayed resolution of the inflammation. Time-restricted feeding (TRF) reduced HF diet-induced weight gain and exacerbation of the inflammatory symptoms, even when started after disease onset. In HF-AL mice, serum leptin levels increased and exhibited a circadian phase shift compared to the NC group, whereas TRF significantly mitigated these alterations. NC-fed db/db mice that produced high levels of leptin exhibited worsened CHS. Blocking the leptin receptors alleviated the inflammatory symptoms in both db/db and HF-AL mice. Extending the analysis to human transcriptomic data and histology suggests that leptin may contribute to pustule formation in non-infectious dermatitis. In summary, our data indicate that both TRF and local inhibition of leptin receptors can individually and in combination serve as effective new tools in managing allergic contact dermatitis.