Long-term obesogenic diet and targeted deletion of potassium channel Kv 1.3 have differing effects on voluntary exercise in mice.

Brandon M Chelette, Abigail M Thomas, Debra Ann Fadool

Physiological reports 2019 Oct

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Voluntary exercise is frequently employed as an intervention for obesity. The voltage-gated potassium channel Kv 1.3 is also receiving attention as a therapeutic target for obesity, in addition to potential therapeutic capabilities for neuroinflammatory diseases. To investigate the combinatorial effects of these two therapies, we have compared the metabolic status and voluntary exercise behavior of both wild-type mice and a transgenic line of mice that are genetic knockouts for Kv 1.3 when provided with a running wheel and maintained on diets of differing fat content and caloric density. We tracked the metabolic parameters and wheel running behavior while maintaining the mice on their assigned treatment for 6 months. Wild-type 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. Similar to previous studies, the Kv 1.3-null mice were resistant to obesity, increased adiposity, and impaired glucose tolerance. Both wild-type and Kv 1.3-null mice maintained on the fatty diet displayed increased wheel running activity compared to control-fed mice, which was caused primarily by a significant increase in the amount of time spent running as opposed to an increase in running velocity. Interestingly, the patterns of running behavior differed between wild-type and Kv 1.3-null mice. Kv 1.3-null mice spent significantly less time running during the light phase and displayed a decrease in running 1-2 h before the onset of the light phase, seemingly in anticipation of the dark-to-light phase transition. 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 Kv 1.3 channel. © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Citation

Brandon M Chelette, Abigail M Thomas, Debra Ann Fadool. Long-term obesogenic diet and targeted deletion of potassium channel Kv 1.3 have differing effects on voluntary exercise in mice. Physiological reports. 2019 Oct;7(20):e14254