Department of Anatomy, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA.
Chicago College of Osteopathic Medicine, Midwestern University, Downers Grove, Illinois, USA.
Physiol Rep. 2024 Dec;12(23):e70140. doi: 10.14814/phy2.70140.
Insufficient physical activity is associated with increased relative risk of cardiometabolic disease and is an independent risk factor for mortality. Experimentally reducing physical activity rapidly induces insulin resistance, impairs glucose handling, and drives metabolic inflexibility. These adaptations manifest during the early stages of physical inactivity, even when energy balance is maintained, suggesting that inactivity-mediated metabolic reprogramming is an early event that precedes changes in body composition. To identify mechanisms that promote metabolic adaptations associated with physical inactivity, we developed a mouse model of physical activity reduction that permits the study of inactivity in animals prior to the onset of overt changes in body composition. Adult mice were randomized into three groups: an inactive control group (standard rodent housing), an active control group (treadmill running 5 d/week for 6-weeks), and an activity reduction group (treadmill running for 4-weeks, followed by 2-weeks of inactivity). Transcriptional profiling of gastrocnemius muscle identified seven transcripts uniquely altered by physical activity reduction compared to the inactive and active control groups. Most identified transcripts had reported functions linked to bioenergetic adaptation. Future studies will provide deeper characterization of the function(s) of each the identified transcripts while also determining how inactivity affects transcriptional regulation in other tissues.
身体活动不足与心血管代谢疾病的相对风险增加有关，是死亡的独立危险因素。实验性地减少身体活动会迅速引起胰岛素抵抗，损害葡萄糖处理能力，并导致代谢灵活性降低。这些适应在身体不活动的早期阶段表现出来，即使能量平衡得到维持，这表明不活动介导的代谢重编程是发生在身体成分变化之前的早期事件。为了确定促进与身体不活动相关的代谢适应的机制，我们开发了一种减少身体活动的小鼠模型，该模型允许在动物出现明显的身体成分变化之前研究不活动。成年小鼠被随机分为三组：不活动对照组（标准啮齿动物饲养）、活动对照组（跑步机每周运行 5 天，持续 6 周）和活动减少组（跑步机运行 4 周，然后不活动 2 周）。比目鱼肌的转录组分析确定了 7 种与不活动和活动对照组相比，由身体活动减少唯一改变的转录本。大多数鉴定出的转录本具有与生物能量适应相关的报道功能。未来的研究将更深入地描述每个鉴定出的转录本的功能，同时确定不活动如何影响其他组织的转录调控。
