Evolution and Plasticity of Muscle Metabolism

肌肉代谢的进化方面还没有得到广泛的研究，尽管适当的燃料底物分配对于有效的运动、产热和全身代谢动态平衡很重要。肌肉燃料使用能力和对环境压力的反应的物种差异，是由于在生理时间尺度上发生的肌肉表型的可塑性(发育和成体可塑性)与基因之间的相互作用所致。我的研究计划的长期目标是了解燃料的传递和利用途径是如何演变的，并对能量和环境压力做出反应，以支持在这个组织中看到的动态能量变化。生活在高海拔地区的动物是研究肌肉代谢对已知的低氧和低温度应激源的进化和可塑性的理想模型。因此，我们使用来自低海拔(LA)和HA种群的不同亲本种群在普通条件下饲养的鹿小鼠(Permyscus Manulatus)。这使我们能够区分基因固定的特征和那些经历环境诱导可塑性的特征。此前，我们已经发现，与低海拔小鼠相比，高原鹿小鼠(I)在更大程度上依赖碳水化合物氧化来进行功率运动，部分原因是进化出的表型可塑性。(Ii)鹿小鼠以高脂肪酸氧化率(FAO)支持产热，HA和LA小鼠的脂肪酸氧化率更高，并显示出强大的表型可塑性。和(Ii)早期生活事件可以影响生存和成年表型，我们发现了鹿小鼠吸热能力如何发展的群体差异，以及出生后寒冷或寒冷和缺氧如何影响成人产热能力。在接下来的5年里，我将解决3个目标，以确定：1.HA运动燃料使用进化差异的潜在机制；2.HA产热过程中粮农组织的调控。3.出生后环境对成虫代谢和产热能力的影响机制。我将使用我们的低海拔和高海拔鹿小鼠来解决这些目标，并利用暴露在慢性低氧或寒冷和低氧中来揭示从属特征的可塑性进化差异，这些差异有助于解释运动或产热性能的适应性差异。通过饲养小鼠至第二代，研究母体照料和环境因素对高原鹿小鼠体温个体发育和产热能力发育可塑性的影响。与传统的啮齿动物模型不同，由此产生的数据可能会揭示出多种不同的生理“解决方案”，使物种要么维持高速率的燃料输送，要么为肌肉提供最佳的燃料分配，以便在低氧气或温度环境中生存。本研究将培养10名理科学士、5名理科硕士。和4名博士生。

The evolutionary aspects of muscle metabolism have not been extensively studied, despite the importance of appropriate fuel substrate allocation for effective locomotion, thermogenesis, and whole-body metabolic homeostasis. Species variation in muscle capacity for fuel use, and the response to environmental stress, results from interactions between genotype and the plasticity of muscle phenotype occurring at physiological time scales (developmental and adult plasticity). The long-term objective of my research program is to understand how fuel delivery and utilization pathways evolve and respond to energetic and environmental stress to support the dynamic energetic changes seen in this tissue. Animals who live in the high altitude (HA) are ideal models to study the evolution and plasticity of muscle metabolism to the known stressors of low oxygen and temperature. Thus, we use deer mice (Peromyscus maniculatus) bred in common conditions from separate parental stocks from populations at low altitude (LA) and HA . This allows us to distinguish genetically fixed traits from those that undergo environmental induced plasticity. Previously, we have found that high altitude deer mice (i) rely to a greater extent in carbohydrate oxidation to power exercise, in part due to evolved phenotypic plasticity to hypoxia compared to low altitude mice. (ii) Deer mice support thermogenesis with high rates of fatty acid oxidation (FAO), which is higher in HA and LA mice and shows robust phenotypic plasticity. and  (ii) Early life events can impact survival and adult phenotypes, and we uncovered population differences in how endothermy develops in deer mice but also in how postnatal cold or cold & hypoxia impact adult thermogenic capacity. In the next 5 years I will address 3 objectives to determine: 1. The underlying mechanisms of evolved differences in exercise fuel use at HA, 2. The regulation of FAO during thermogenesis at HA. and 3. The mechanisms responsible for postnatal environment impacts on adult metabolism and thermogenic capacity. I will address these objectives using our low and high altitude deer mice, and use exposures to chronic hypoxia or cold & hypoxia to uncover evolved differences in plasticity of subordinate traits that help explain adaptive differences in locomotory or thermogenic performance. Through breeding mice to the second generation we will study maternal care and environmental effects on the ontogeny of endothermy and the developmental plasticity of thermogenic capacity in high altitude deer mice. Unlike traditional rodent models, resulting data may uncover multiple different physiological "solutions" allowing species to either sustain high rates of fuel delivery, or to provide the optimal allocation of fuel to muscle for survive in low O2 or temperature environments. This research will train 10 B.Sc, 5 M.Sc. and 4 Ph.D. students.