Natural killer cell subset count and antigen-stimulated activation in response to exhaustive running following adaptation to a ketogenic diet

Abstract

New findings: What is the central question of this study? Does a ketogenic diet (KD) modulate circulating counts of natural killer (NK) cells, including CD56^bright and CD56^dim subsets, and their ability to activate (CD69 expression) following in vitro antigen stimulation in response to exhaustive moderate-intensity exercise? What is the main finding and its importance? The KD amplified the biphasic exercise-induced NK cell response due to a greater mobilisation of the cytotoxic CD56^dim subset but did not alter NK cell CD69 expression. The KD appears to modulate exercise-induced circulating NK cell mobilisation and egress, but not antigen-stimulated circulating NK cell activation.

Abstract: We investigated the effect of a 31-day ketogenic diet (KD) compared with a habitual, carbohydrate (CHO)-based diet on total circulating natural killer (NK) CD3^- CD56⁺ , dim and bright subset count, and antigen-stimulated CD3^- CD56⁺ cell activation (CD69⁺ ) in response to exhaustive running. In a randomised, repeated-measures, cross-over study, eight trained, male endurance athletes ingested a 31-day low-CHO KD or their habitual diet (HD). On day 31, participants ran to exhaustion at 70% ${\dot{V}}_{O_2\max }$ (∼3.5-4 h, ∼45-50 km). A low-CHO (<10 g) meal was ingested prior to the KD trial, with fat ingested during exercise. A high-CHO (2 g kg^-1 ) meal was ingested prior to the HD trial, with CHO (∼55 g h^-1 ) ingested during exercise. Venous blood samples were collected at pre-exercise, post-exercise and 1 h post-exercise. The KD amplified the classical exercise-induced biphasic CD3^- CD56⁺ cell response by increasing the post-exercise counts (P = 0.0004), which appeared to be underpinned by the cytotoxic CD3^- CD56^dim subset (main effect of time point, P < 0.0001). The KD had no effect on NK cells' expression of CD69 or their geometric mean fluorescence intensity of CD69 expression, either for unstimulated or for antigen-stimulated NK cells (all P > 0.05). In conclusion, adaptation to a KD may alter the number of circulating NK cells but not their ability to activate to an antigenic challenge.

Keywords: CD56; CD69; endurance; exercise; flow cytometry; ketosis; lymphocytes.