Exercise Training Attenuates CD8 T cell Exhaustion, But Not Glucose Intolerance, Following Weight Cycling

Obesity increases the risk of glucose intolerance and CD8 T cell exhaustion, which indicates an impaired immune function. While weight loss mitigates these risks, most individuals regain weight (weight cycling), which worsens both conditions. Exercise training protects against glucose intolerance and attenuates T cell exhaustion, but its protective role during weight cycling remains unclear. PURPOSE: The purpose of this study was to examine whether exercise training can prevent glucose intolerance and attenuate CD8 T cell exhaustion following weight cycling in mice. METHODS: Forty-eight C57Bl/6 mice were used for the study. Lean and obese groups were elicited using diet. Weight cycle (WC) and Weight cycle and exercise (WC+EX) groups were put through 3 cycles of 9 weeks diet, with the WC+EX group subjected to voluntary wheel running during weight loss. Body weight, food intake, and body composition (MRI) were assessed, and glucose tolerance was evaluated at week 26. At week 27, epididymal adipose tissue was collected, and CD8+ T cells resident in fat pad were analyzed via flow cytometry for exhaustion. One-way ANOVA was used to assess differences in glucose levels and CD8 Tcell exhaustion markers (TOX, PD1) between groups. RESULTS: At week 27, there was a significant difference in the body weight of mice in the different groups (P =CONCLUSION: These results suggest that Exercise attenuates CD8 T cell exhaustion, but not glucose intolerance, following weight cycling.