Abstract

Recent evidence implicates chemokine (C-C motif) ligand 5 (CCL5, also known as RANTES) and its receptor CCR5 in mediating T cell infiltration into adipose and other tissues, which contributes to chronic low-grade inflammation in obesity and type 2 diabetes (T2D). Exercise may relieve obesity-related inflammation but the effects of interval training on T-cell migration and tissue infiltration in T2D are unknown. PURPOSE: To examine the impact of interval walking training (IWT) versus continuous walking training (CWT) on circulating RANTES along with T cell and adipose tissue CCR5 in patients with T2D. METHODS: Participants with T2D were randomized to control (n=8), IWT (n=12) or CWT (n=12). Training groups were prescribed five 60-minute sessions per week of free-living training with intensity monitored with an accelerometer and heart rate monitor. Fasting blood samples and subcutaneous abdominal adipose tissue biopsies were obtained before and 6 days after completion of the 16-week intervention period. Plasma RANTES was measured by ELISA. Peripheral blood mononuclear cells (PBMCs) were isolated for subsequent measurement of CD8+ T cell CCR5 surface protein expression using flow cytometry. mRNA expression of RANTES, CCR5 and CD8 were measured in subcutaneous adipose tissue biopsy samples by qPCR. RESULTS: Training duration and mean intensity were well-matched between IWT and CWT. A significant group X time interaction (p<0.05) was detected for CD8+ T cell CCR5 surface protein expression, with post-hoc tests revealing a reduction of ~20% after IWT (p<0.05) with no changes seen in CWT or control. Plasma RANTES concentration and adipose tissue mRNA expression of RANTES, CCR5 and CD8 were not altered in IWT, CWT, or control groups following the intervention period (all p>0.05). CONCLUSIONS: Sixteen weeks of IWT, previously shown to benefit physical fitness, insulin sensitivity, body composition, and glycemic control in patients with T2D, resulted in lower CD8+ T cell CCR5 protein expression. These findings suggest lower migratory potential for circulating T cells but future research is needed to determine if IWT influences infiltration of T cells into adipose and other tissues. JPL is funded by a CIHR New Investigator Award (MSH-141890)

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