Obesogenic diet and targeted deletion of potassium channel Kv1.3 have differing effects on voluntary exercise in mice.

Abstract

Voluntary exercise is frequently employed as an intervention for obesity. The voltage-gated potassium Kv1.3 is also receiving attention as a therapeutic target for obesity, in addition to potential therapeutic capabilities for neuroinflammatory diseases. To investigate combinatorial effects of these two therapies, we have compared the metabolic status and voluntary exercise behavior of both wildtype mice and a transgenic line of mice that are genetic knockouts for Kv1.3 when provided with a running wheel and maintained on diets of differing fat content and caloric density. We tracked metabolic parameters and wheel running behavior while maintaining the mice on their assigned treatment for 6 months. Wildtype mice maintained on the fatty diet gain a significant amount of bodyweight and adipose tissue and display significantly impaired glucose tolerance, though all these effects were partially reduced with provision of a running wheel. Similarly to previous studies, the Kv1.3-null mice were resistant to obesity, increased adiposity, and impaired glucose tolerance. Both wildtype and Kv1.3-null mice maintained on the fatty diet displayed increased wheel running activity compared to CF-fed mice which was caused primarily by a significant increase in amount of time spent running as opposed to an increase in running velocity. Interestingly, the patterns of running behavior differ between wildtype and Kv1.3-null mice, especially in how their resting periods are distributed through the dark phase. These studies indicate that voluntary exercise combats metabolic maladies and running behavior is modified by both consumption of an obesogenic diet and deletion of the Kv1.3 channel.\n\nNEW and NOTEWORTHYO_LIKv1.3-null mice exhibit different running and resting patterns compared to wildtype mice\nC_LIO_LIMice maintained on an obesogenic diet (32% kcal from fat) exhibit increased running distance and increased time spent running compared to mice fed normal rodent chow.\nC_LI