Chelette Brandon M, Thomas Abigail M, Fadool Debra Ann
Department of Biological Science, The Florida State University, Tallahassee, Florida.
Programs in Neuroscience, The Florida State University, Tallahassee, Florida.
Physiol Rep. 2019 Oct;7(20):e14254. doi: 10.14814/phy2.14254.
Voluntary exercise is frequently employed as an intervention for obesity. The voltage-gated potassium channel K 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 K 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 K 1.3-null mice were resistant to obesity, increased adiposity, and impaired glucose tolerance. Both wild-type and K 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 K 1.3-null mice. K 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 K 1.3 channel.
自愿运动经常被用作治疗肥胖的一种干预手段。电压门控钾通道K 1.3除了对神经炎症性疾病具有潜在治疗能力外，作为肥胖的治疗靶点也受到关注。为了研究这两种治疗方法的联合效果，我们比较了野生型小鼠和K 1.3基因敲除的转基因小鼠品系在提供跑步机并给予不同脂肪含量和热量密度饮食时的代谢状态和自愿运动行为。我们在让小鼠接受指定治疗6个月的过程中跟踪其代谢参数和跑步机跑步行为。食用高脂肪饮食的野生型小鼠体重和脂肪组织显著增加，葡萄糖耐量明显受损，不过提供跑步机后所有这些影响都有所减轻。与之前的研究相似，K 1.3基因敲除小鼠对肥胖、肥胖增加和葡萄糖耐量受损具有抗性。与喂食对照饮食的小鼠相比，食用高脂肪饮食的野生型和K 1.3基因敲除小鼠的跑步机跑步活动都增加了，这主要是由于跑步时间显著增加，而不是跑步速度增加。有趣的是，野生型和K 1.3基因敲除小鼠的跑步行为模式不同。K 1.3基因敲除小鼠在光照阶段跑步时间明显减少，并且在光照阶段开始前1 - 2小时跑步量减少，似乎是在预期从黑暗到光照阶段的转变。这些研究表明，自愿运动可以对抗代谢疾病，而致肥胖饮食的摄入和K 1.3通道的缺失都会改变跑步行为。
