Inactivity-mediated molecular adaptations: Insights from a preclinical model of physical activity reduction.

IF 2.2 Q3 PHYSIOLOGY Physiological Reports Pub Date : 2024-12-01 DOI:10.14814/phy2.70140
Alice Meyer, Nicole Kim, Melissa Nguyen, Monica Misch, Kevin Marmo, Jacob Dowd, Christian Will, Milica Janosevic, Erin J Stephenson
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Abstract

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.

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不活动介导的分子适应:来自身体活动减少的临床前模型的见解。
体力活动不足与心脏代谢疾病的相对风险增加有关,是死亡的独立危险因素。实验表明,减少体力活动会迅速诱导胰岛素抵抗,损害葡萄糖处理,并导致代谢不灵活。这些适应在身体不活动的早期阶段表现出来,即使在维持能量平衡的情况下也是如此,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。为了确定促进与缺乏运动相关的代谢适应的机制,我们开发了一个减少身体活动的小鼠模型,该模型允许在身体成分发生明显变化之前研究动物的缺乏运动。成年小鼠随机分为三组:不活动对照组(标准啮齿动物住房),活动对照组(每周跑步5天,持续6周)和活动减少组(跑步4周,随后2周不活动)。对腓肠肌的转录谱分析发现,与不运动和运动对照组相比,体育活动减少导致了7个转录本的独特改变。大多数鉴定的转录本具有与生物能量适应相关的功能。未来的研究将提供每个已鉴定转录本功能的更深入的特征,同时也确定不活跃如何影响其他组织的转录调节。
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来源期刊
Physiological Reports
Physiological Reports PHYSIOLOGY-
CiteScore
4.20
自引率
4.00%
发文量
374
审稿时长
9 weeks
期刊介绍: Physiological Reports is an online only, open access journal that will publish peer reviewed research across all areas of basic, translational, and clinical physiology and allied disciplines. Physiological Reports is a collaboration between The Physiological Society and the American Physiological Society, and is therefore in a unique position to serve the international physiology community through quick time to publication while upholding a quality standard of sound research that constitutes a useful contribution to the field.
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