Metabolic Adaptation to Chronic Hypobaric Hypoxia: PET Study

利用自然耐受有限氧气供应的生物来探索自然界对缺氧的分子和代谢防御策略是生物学中一个久经考验的实验范式。我们在最近的研究中发现，现在低地人的后裔。在这些受试者的心脏和大脑葡萄糖代谢的先导位置发射断层扫描（PET）研究中，我们发现生物医学适应被用来维持每个器官的能量平衡，尽管他们的家庭环境是强制性的和慢性的缺氧。心脏数据显示，即使在禁食一夜之后，基础能量需求也明显依赖葡萄糖。这暂时被解释为一种适应，用于最大限度地提高每单位氧气可获得的有用能量。有趣的是，在海平面上生活了仅仅20天之后，这些研究对象部分地，甚至在一个案例中完全地，转向了对基质的正常偏好模式。脑葡萄糖摄取水平处于正常范围的极端上端，可能表明至少有一些非氧依赖性代谢来维持能量平衡。由于对适应性反应的控制和操纵可能具有巨大的实际重要性，因此必须确定这些防御机制是否适用于人类物种。出于这个原因，我们建议将我们的研究扩展到包括尼泊尔的夏尔巴人在内的研究对象，这些研究对象在基因和个体上都被认为是适应缺氧的。

The use of organisms that are naturally tolerant to limiting supplies of oxygen to probe nature's molecular and metabolic defense strategies against hypoxia is a tried and tested experimental paradigm in biology. We have found in recent studies that the present day descendent of the lowlanders. In pilot position emission tomography (PET) studies of glucose metabolism in heart and brain in these subjects, we found that biomedical adaptations were utilized in order to maintain each organ in energy balance despite the imposed and chronic hypoxia of their home environments. The heart data demonstrated a significant dependence on glucose for basal energy needs, even following an overnight fast. This provisionally has been interpreted as an adaptation, serving to maximize the amount of useful energy obtainable per unit amount of oxygen. Interestingly, the subjects resolved partially, and in one case entirely, to the normal pattern of substrate preference after only 20 days living at sea level. Brain uptake levels of glucose were at the extreme upper end of the normal range and may indicate at least some non-oxygen dependent metabolism to maintain energy balance. Because control and manipulation of the adaptive response could be of immense practical importance, it is imperative to ascertain if these defense mechanisms are general to the human species. For that reason, we propose to extend our study to include subjects that would be expected both genetically and individually also to be hypoxia-adapted, the Sherpas of Nepal.