Time restricted feeding in diet induced obesity restores diurnal T cell rhythms in the small intestine

Abstract

Abstract Diet induced obesity (DIO) causes circadian disruption and dysregulation of T cells in the gut. Previous studies have also shown that immune cells, including T cells, have rhythms of migration through tissues. We previously found that time-restricted feeding (TRF) in DIO leads to reduced cardiovascular target organ damage. However, it is unknown how TRF in DIO alters intestinal T cells, specifically anti-inflammatory regulatory T cells (FoxP3) and inflammatory Th17 cells (RORgt). We used a 20-week model of high fat (DIO) with TRF intervention with food restricted to the 12-hour active (dark) phase in weeks 18–20. We assessed T cells in the small intestine via flow cytometry in normal diet (ND), DIO, and DIO+TRF groups at Zeitgeber time (ZT) 3 (light period) and ZT13 (dark period). Interestingly, there is a significant diurnal difference of total immune cells (CD45 +), total T cells (TCRb +), and CD4 +T cells in the small intestine of ND mice, with increases at ZT13 compared to ZT3. No diurnal rhythm in T cells is seen in DIO mice. DIO+TRF restores a significant time-of-day difference in T cellsin the small intestine. We investigated CD4 +T cell transcription factors, RORgt and Foxp3. RORgt expression was suppressed at ZT13 compared to ZT3 in DIO. DIO+TRF led to increased RORgt +CD4 +T cells at ZT13 compared to ZT3. The number of Foxp3 +CD4 +T cell was also increased at ZT13 compared to ZT3 in DIO+TRF. CXCR3, a T cell migration marker, was found to be significantly downregulated on CD4 +T cells at ZT13 compared to ZT3 in DIO+TRF mice but not DIO. These findings indicate that intestinal T cell rhythms are lost in DIO mice and TRF restores the T cell rhythm and suggest that the TRF-induced restoration of T cell rhythms in the gut may lead to reduced target organ damage.