Molecular Sciences IV.
Zsófia Búr, Ágnes Sűdy, Zalán Lumniczky, Máté Szekér, Bernadett Vendl, Csongor Szántó, Bence Koós, Krisztina Káldi, Krisztina Ella
Department of Physiology, Semmelweis University, Budapest
Introduction: The circadian rhythm controls many physiological processes including metabolism and immune responses. Metabolic disorders associated with low-grade inflammation and several immune functions are negatively affected by circadian disturbances. Our previous experimental data support that time-restricted feeding (TRF) enhances metabolic rhythm and modifies leukocyte responsiveness. Taking this together, the experimental interrogation of how rhythmic feeding affects inflammation development may help to identify new supportive therapy forms for the treatment of autoimmune diseases.
Aims: We aimed to investigate a short-term (4 weeks) high-fat (HF) diet to initiate metabolic aberration in a mouse model. We will also examine how a high-fat diet with TRF influences metabolic and immune functions.
Methods: HF food was constantly available in the ad libitum group, while in the TRF group, the food access was restricted to 10 hours during the active phase of the animals (ZT 12-22). We had a control group fed with normal chow, ad libitum. We collected blood samples to determine leukocyte counts and identify leukocyte subgroups with flow cytometry. We measured clock and adipokine gene expression in peripheral tissues using qPCR, and determined serum leptin level with ELISA. KBxN serum transfer arthritis was used to induce joint inflammation as a model of acute phase of human rheumatoid arthritis. Six days after induction, we measured IL1b levels and determined neutrophil counts in digested hind limbs.
Results: HF diet altered the rhythm of leukocyte counts in the blood, especially that of neutrophils and monocytes. Both in the white adipose tissue (WAT) and in the bone marrow, clock genes' expressions were increased by the HF diet. Leptin gene expression in WAT and serum leptin levels were highly increased in the HF group but TRF slackened the rise in leptin. In addition, TRF dampened the symptoms of autoinflammatory arthritis and neutrophil counts decreased in hind limbs compared to ad libitum on the sixth day.
Conclusion: Our data suggest that TRF can counteract with the development of short-term, diet-induced metabolic disturbances, and can be an effective tool in the therapy of inflammatory diseases as well.
Funding: OTKA (132393), TKP-EGA-25, SE250+