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，尽管有效的运动，产热和全身代谢稳态的重要性，适当的燃料基板分配。肌肉的燃料利用能力的物种差异，以及对环境压力的反应，从基因型和肌肉表型的可塑性发生在生理时间尺度（发育和成人可塑性）之间的相互作用的结果。我的研究计划的长期目标是了解燃料输送和利用途径如何演变和响应能量和环境压力，以支持在该组织中看到的动态能量变化。高原动物是研究低氧和低温应激条件下肌肉代谢演变和可塑性的理想模型。因此，我们使用鹿小鼠（Peromyscus maniculatus）在普通条件下繁殖，从不同的亲本股票在低海拔（LA）和HA的人口。这使我们能够区分遗传固定的性状和那些经历环境诱导可塑性的性状。 以前，我们已经发现，高海拔鹿小鼠（i）在更大程度上依赖于碳水化合物氧化来为运动提供动力，部分原因是与低海拔小鼠相比，进化的表型可塑性对缺氧。(ii)鹿小鼠支持产热与高速率的脂肪酸氧化（FAO），这是更高的HA和LA小鼠，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，我们发现了鹿鼠中内温性如何发展以及出生后寒冷或寒冷缺氧如何影响成年产热能力的群体差异。在未来的5年里，我将致力于确定3个目标：1。HA运动燃料使用差异的潜在机制，2。FAO在HA产热过程中的调节。和3.出生后环境影响成年代谢和产热能力的机制。我将使用我们的低海拔和高海拔鹿小鼠来解决这些目标，并使用暴露于慢性缺氧或寒冷和缺氧来揭示从属性状可塑性的进化差异，这些差异有助于解释运动或产热性能的适应性差异。本研究拟通过对高原鹿鼠进行第二代繁殖，研究母畜照料和环境因素对高原鹿鼠内温性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，所得到的数据可能会揭示多种不同的生理“解决方案”，使物种能够维持高速率的燃料输送，或为肌肉提供最佳的燃料分配，以便在低O2或温度环境中生存。本研究将培养B.Sc 10名，M. Sc 5名，Ph.D. 4名。学生

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.