Molecular Sciences I. (Poster discussion will take place in the Aula during the Coffee Break)
Krisztina Ella, Ágnes Sűdy, Zsófia Búr, Bence Koós, Ármin Szabolcs Kisiczki, Zalán Lumniczky, Krisztina Káldi
Department of Physiology, Semmelweis University, Budapest
Introduction: The circadian rhythm regulates basic physiological processes including metabolism and immune functions. It is well-known, that food intake entrains the circadian clock in certain peripheral tissues and parallel alters the metabolic rhythm. In line with this, irregular timing of food intake leads to disruption of the metabolic rhythm. Metabolic disturbances (like diabetes mellitus or obesity) are usually associated with changes in inflammatory responses.
Aims: Our previous experiments showed, that timed feeding increases the amplitude of the oscillation of blood leukocyte count and dampens autoimmune responses. Our aim was to investigate whether feeding rhythm affects cell populations and the inflammatory state in the bone marrow and the spleen which are intensively involved in the homing of leukocytes.
Methods: Two feeding schedules were set in a mouse model. In the ad libitum (AL) group food was constantly available, whereas in the time restricted feeding (TRF) group food availability was limited to the first 10 hours of the active phase of mice. Bone marrow and spleen samples were isolated after 4 weeks conditioning. Absolute leukocyte counts and percentage of leukocyte subsets were determined by flow cytometry. RNA was extracted from the samples, then cDNA was synthetized and the relative clock (per2, reverbA) and inflammatory (il-6, tnfA, il-1B, nlrp3) gene expressions were measured with RT-qPCR.
Results: TRF induced robust metabolic rhythm, whereas AL decreased the rhythmic gene expression in peripheral tissues. In the TRF group neutrophil levels in the bone marrow (but not in the spleen) changed according to the cell count rhythm in the blood. In addition, in the AL group the neutrophil count was markedly elevated at the beginning of the active phase. TRF increased the amplitude of time-dependent clock gene expression in different tissues. In the spleen both the oscillation and the average levels of pro-inflammatory cytokines were enhanced.
Conclusion: TRF modifies the rhythmic functions in both the bone marrow and the spleen, and therefore might contribute to the milder reactivity of the immune system. Our observations suggest that timed food intake could be effective as a supplementary therapy in autoinflammatory diseases.
Funding: EFOP-3.6.3-VEKOP-16-2017-00009, OTKA 108382, 132393, ÚNKP-20-4-II-SE-23, FIKP, STIA-18, TKP-EGA-25