PhD Scientific Days 2024

Molecular Medicine II.

Time-Restricted Feeding Prevents Adverse Effects of High-Fat Diet in Contact Hypersensitivity Model

Text of the abstract

Background: Different diets, like caloric restriction, AIP (autoimmune protocol), Mediterranean, and ketogenic, are recommended for patients suffering from autoimmune diseases as a complementary therapeutic option. However, these dietary interventions require high patient adherence because they are based on caloric restriction or changes in nutrient composition. Additionally, autoimmune diseases are often associated with metabolic disorders. Therefore, the development of new, more sustainable dietary approaches is needed. Our previous data indicated that time-restricted feeding (TRF) enhances the rhythm of metabolism and benefits immune reactivity. We also showed that TRF mitigates symptoms’ severity in autoimmune arthritis.
Objective: Our aim was to investigate how rhythmic feeding and nutrients with high-fat content affect inflammation development in a contact hypersensitivity (CHS) model.
Methods: We used three feeding schedules in mice. The metabolic disturbance was triggered with ad libitum high-fat diet (HF), whereas the HF-TRF group had food access limited to the first 10 hours of the active phase of the animals. The control group had constant access to normal chow (N). CHS was induced after four weeks of conditioning to the different feeding programs. Ear swelling was assessed daily, and tissue samples were collected.
Results: The HF group increased caloric intake compared to the N group. However, TRF does not influence caloric intake during four weeks of conditioning. After four weeks, as a metabolic marker, leptin was measured. Elevated serum leptin level was detected in the HF group compared to the N and HF-TRF groups. In the CHS model, the HF diet aggravated the inflammation response and prolonged the regeneration; the HF group had significantly increased ear thickness, leukocyte infiltration, and IL-1B levels compared to the N group. CHS severity of the HF-TRF group was significantly reduced compared to the HF group, and a compensatory effect of TRF on HF diet-induced inflammation was observed in all indicative parameters.
Conclusion: Our study suggests that TRF could counteract the development of diet-induced metabolic disturbances, ameliorate inflammatory disease severity, and shorten the duration of regeneration.
Funding: NKFIH (K132393), TKP-EGA-25, SE250+, ÚNKP-20-4-II-SE-23 and ÚNKP-23-5-SE-20