TIME-RESTRICTED FEEDING PREVENTS THE DETRIMENTAL EFFECTS OF A HIGH-FAT DIET UNDER BOTH HOMEOSTATIC AND INFLAMMATORY CONDITIONS
Búr Zsófia
Molecular Medicine Division
Dr. Várnai Péter
SE Élettani Intézet könyvtára
2025-12-11 14:00:00
Cellular and Molecular Physiology
Dr. Hunyady László
Dr.Káldi Krisztina, Dr.Ella Krisztina
Dr. Dóra Dávid
Dr. Szabó Áron
Dr. Hegedűs Tamás
Dr. Hricisák László
Dr. Kemény Ágnes
In modern societies, irregular and unhealthy eating patterns are increasingly prevalent, contributing to the development of both metabolic and inflammatory disorders. Restricting food access to a specific time window of the day, even without reducing caloric intake, entrains peripheral clocks and enhances metabolic rhythm. Timed food intake represents an affordable and well-tolerable approach that is beneficial for both the prevention and treatment of metabolic diseases. Bidirectional communication between metabolism and immunity suggests that time-restricted eating may serve as a complementary therapy for inflammatory diseases as well.
We addressed the metabolic effect of different feeding regimens, like ad libitum (AL) and time-restricted feeding (TRF) subjected to both normal chow (NC) and high-fat (HF) diet under steady-state conditions. HF-AL impairs metabolic state, leads to excessive body mass increase, elevated fasting glucose levels, phase-shifted corticosterone rhythms, and increased serum leptin levels. HF-TRF partially prevents these negative effects, potentially through the synchronization of the white adipose tissue clock.
We investigated how the timing of food intake influences K/BxN serum-transfer arthritis (STA) and contact hypersensitivity (CHS), a mouse model of human rheumatoid arthritis (RA) and allergic contact dermatitis (ACD), respectively. Inflammation was analyzed at the macroscopic, tissue, and cellular levels. In the group with AL food access, the HF diet worsened the inflammatory response, as indicated by increased inflammatory swelling, neutrophil infiltration, IL-1β, and leptin levels compared to NC conditions. NC-fed db/db mice that produced high levels of leptin exhibited worsened CHS. Moreover, blocking the leptin receptors alleviated the phenotypic and molecular signs of inflammation in db/db, as well as in HF-AL mice.
Our data indicate that HF diet and prolonged daily eating periods can exacerbate inflammatory responses in various disease models. According to our model, leptin might contribute to the pathogenesis by promoting the activity of circulating myeloid cells via increasing adhesion molecule expression under steady-state conditions and enhancing their migratory capacity under inflammatory conditions. Based on our results, the inflammation-attenuating effect of both TRF and local inhibition of leptin receptors may offer promising therapeutic strategies for managing RA and ACD.
