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

BackgroundIn modern societies, irregular and unhealthy eating behavior is increasingly prevalent, contributing to the development of both metabolic and inflammatory disorders. 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 influences the severity of contact hypersensitivity (CHS), a murine model of human allergic contact dermatitis which affects approximately 20% of the population. MethodsMice were fed with normal (NC) or high-fat (HF) chow under ad libitum (AL) or 10/14 time-restricted feeding (TRF). CHS severity was analyzed at macroscopic, tissue and cellular levels in both mild (acute) and severe (subacute) forms of the disease. To assess the mediator role of leptin, we used db/db mice, inhibited leptin signaling and analyzed human transcriptomic data. ResultsUnder conditions with ad libitum (AL) food access, HF diet resulted in impaired metabolic state and a more severe form of inflammation. Increased ear thickness, leukocyte infiltration, pustule formation, IL-1{beta}, CXCL2 levels and markedly delayed resolution of the inflammation were observed in HF-AL animals. 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 were elevated and displayed a phase-shifted diurnal pattern compared to the NC group, whereas TRF markedly attenuated these changes. 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 patients transcriptomic data and histology suggests that leptin may contribute to pustule formation in non-infectious dermatitis in humans. ConclusionsOur 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.