Kaldi, K. | bioRxiv Science

bioRxiv2025

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

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.

immunology↗

bioRxiv2022

Adaptation to starvation requires a flexible circadian clockwork in Neurospora crassa

The circadian clock governs rhythmic cellular functions by driving expression of a substantial fraction of the genome and thereby significantly contributes to the adaptation to changing environmental conditions. Using the circadian model organism Neurospora crassa, we show that molecular timekeeping is robust even under severe limitation of carbon sources, however, stoichiometry, phosphorylation and subcellular distribution of the key clock components display drastic alterations. Protein kinase A, protein phosphatase 2A and glycogen synthase kinase are involved in the molecular reorganization of the clock. RNA-seq analysis reveals that the transcriptomic response of metabolism to starvation is highly dependent on the positive clock component WC-1. Moreover, our molecular and phenotypic data indicate that a functional clock facilitates recovery from starvation. We suggest that the molecular clock is a flexible network that allows the organism to maintain a rhythmic physiology and preserve fitness even under long-term nutritional stress.

cell biology↗