Regulatory changes contribute to the adaptive enhancement of thermogenic capacity in high-altitude deer mice
Regulatory changes contribute to the adaptive enhancement of thermogenic capacity in high-altitude deer mice
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DOI：
10.1073/pnas.1120523109
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发表时间：
2012-05-29
影响因子：
11.1
通讯作者：
Storz, Jay F.
中科院分区：
文献类型：
--
作者：
Cheviron, Zachary A.;Bachman, Gwendolyn C.;Storz, Jay F.
为了应对缺氧应激，许多动物通过抑制总代谢来补偿细胞O-2供应的减少，从而减少O-2需求。对于原产于高海拔环境的小型吸热动物来说，这并不总是一种可行的策略，因为持续有氧产热的能力对于长期寒冷胁迫期间的生存至关重要。例如，对鹿鼠（Peromyscus maniculatus）的生存研究表明，在高海拔地区，产热能力受到强烈的定向选择。在这里，我们整合的措施，整个有机体产热性能与代谢酶活性和基因组转录谱的措施，以研究适应性变化的机制基础，在这个复杂的性状在鹿鼠是本地不同海拔。我们证明，高原鹿小鼠有一个增强的产热能力相比，在缺氧的低地同种和密切相关的低地物种，白足鹿。我们的研究结果表明，高原鹿小鼠产热性能的增强主要归因于氧化脂质作为主要代谢燃料来源的能力增加。这种有氧产热能力的增强与肌肉代谢酶的活性升高有关，这些酶影响高海拔鹿鼠通过脂肪酸氧化和氧化磷酸化途径的通量，并伴随着这些相同途径中基因表达的变化。与来自高海拔地区人类研究的预测相反，我们的研究结果表明，在缺氧条件下维持长时间产热的选择促进了代谢燃料使用的转变，有利于脂质而不是碳水化合物。
In response to hypoxic stress, many animals compensate for a reduced cellular O-2 supply by suppressing total metabolism, thereby reducing O-2 demand. For small endotherms that are native to high-altitude environments, this is not always a viable strategy, as the capacity for sustained aerobic thermogenesis is critical for survival during periods of prolonged cold stress. For example, survivorship studies of deer mice (Peromyscus maniculatus) have demonstrated that thermogenic capacity is under strong directional selection at high altitude. Here, we integrate measures of whole-organism thermogenic performance with measures of metabolic enzyme activities and genomic transcriptional profiles to examine the mechanistic underpinnings of adaptive variation in this complex trait in deer mice that are native to different elevations. We demonstrate that highland deer mice have an enhanced thermogenic capacity under hypoxia compared with lowland conspecifics and a closely related lowland species, Peromyscus leucopus. Our findings suggest that the enhanced thermogenic performance of highland deer mice is largely attributable to an increased capacity to oxidize lipids as a primary metabolic fuel source. This enhanced capacity for aerobic thermogenesis is associated with elevated activities of muscle metabolic enzymes that influence flux through fatty-acid oxidation and oxidative phosphorylation pathways in high-altitude deer mice and by concomitant changes in the expression of genes in these same pathways. Contrary to predictions derived from studies of humans at high altitude, our results suggest that selection to sustain prolonged thermogenesis under hypoxia promotes a shift in metabolic fuel use in favor of lipids over carbohydrates.