The Impact of Time-Restricted Feeding on Exercise-Induced Immune Parameters in C57BL/6 Male Mice

Abstract

Objectives Food intake and exercise are considered modulators of the immune system. Specifically, intermittent fasting protocols have been demonstrated to reduce inflammation and alter cytokine responses. The objective of the current study was to determine if a form of intermittent fasting known as time-restricted feeding (TRF) would alter immune parameters in response to exercise. Methods 8-week-old C57BL/6 male mice were divided into three groups based on feeding schedule; group one had access to food ad libitum (Control) and groups two and three had access to food in a time restricted manner. Access was allowed for six hours per day either immediately after running (TRF-imm) or six hours after running (TRF-del). Mice ran on a treadmill for 1 hour, 5 days per week for eight weeks. Diet consisted of 21% protein, 16% fat and 64% carbohydrate. Weight, glucose and ketone levels, and immune populations were analyzed. Systemic IL-6 and TNF-α levels were measured before and after running. In a subpopulation, cytokine response to lipopolysaccharides (LPS) was also monitored. Results All mice gained weight during the eight-week intervention, but TRF-imm gained significantly less weight than Control (P = 0.02). No differences were detected in glucose levels. The ketone body β-hydroxybutyrate (BHB) was significantly higher at week eight in TRF groups (P ≤ 0.03) but running induced BHB in all groups to approximately 1 mM. Running reduced the blood lymphocytes levels (P < 0.05), with a concomitant increase of granulocytes (P < 0.05) in all groups. There was a small increase in monocytes only in the Control group (P = 0.017). No differences were detected in splenic immune populations, including CD4 and CD8 T cells, and CD11b + cells. Both IL-6 and TNF-α levels were low in all groups before exercise; however, post exercise IL-6 was increased, but not to the same extend in all groups. The IL-6 response was blunted in the TRF groups. The reduced levels of IL-6 was not due to loss of immune function, as both IL-6 and TNF-α were readily induced by exposure of mice to LPS. Conclusions Time-restricted feeding protocols did not induce differences in immune cell composition in blood or spleen but resulted in attenuated exercise-induced IL-6 levels. Funding Sources University of Memphis, School of Health Studies.