Abstract 127: Time Restricted Feeding in Diet Induced Obesity Reduces Kidney Cd8 + T Cells

Diet induced obesity (DIO) is one of the leading risk factors for chronic kidney disease. Previous studies identified a role for pro-inflammatory T cells in mediating DIO-driven renal damage. We found that time restricted feeding (TRF; food available only in 12-hr dark phase) during the final 2 weeks of a 20-week DIO model (45% fat) significantly improves renal damage compared to DIO ad libitum fed male mice. DIO+TRF also significantly reduced total T cells in the kidney adjacent to vasa recta in the outer medulla compared to DIO ad libitum mice assessed at the start of the dark phase or Zeitgeber Time (ZT) 12. We hypothesized that DIO+TRF decreases renal and circulating pro-inflammatory CD4 + and CD8 + T cells compared to DIO ad libitum in a time-of-day dependent manner . Using flow cytometry, we found that DIO significantly increases total renal T cells compared to normal diet (ND; 10% fat) at ZT13-15 (dark phase) only. DIO+TRF significantly decreases total renal T cells compared to DIO in the dark phase (n=7-14; 2-way ANOVA, Interaction: p=0.016, Effect of Time of Day: p=0.010, Effect of Diet: p=0.001). Our data showed no significant changes in renal T cell numbers in the light phase. Compared to ND, DIO increased renal CD8 + T cells at ZT13-15 and DIO+TRF normalized renal CD8 + T cells (n=7-14; 2-way ANOVA, Interaction: p=0.007, Effect of Diet: p=0.004). DIO and DIO+TRF did not alter renal CD4 + T cells at either ZT1-3 or ZT13-15 compared to ND. We further examined the kidney CD8 + T cell phenotype with DIO and TRF. We also found no significant changes in CD8 + T cell activation markers, perforin and granzyme B, CD8 + T cell development marker EOMES, or CD8 + T cell pro-inflammatory cytokines, IFNγ and TNFα. We assessed circulating CD8 + and CD4 + T cells via flow cytometry to analyze systemic effects of TRF. DIO+TRF led to a diurnal rhythm of CD8 + T cells with increased circulating CD8 + T cells in the dark phase compared to the light phase that was not observed in the ND or DIO groups (n=7-17; 2-way ANOVA, Interaction: p=0.012). No significant changes were observed in circulating CD8 + T cell activation markers or cytokines. DIO and TRF had no significant effect on numbers of circulating CD4 + T cells. We conclude that DIO+TRF influences rhythms of circulating and renal CD8 + T cells, but not CD4 + T cells.