Metabolic Adaptation to Chronic Hypobaric Hypoxia: PET Study

利用自然耐受氧气供应的生物体来探索自然界对抗缺氧的分子和代谢防御策略，是生物学中经过验证和测试的实验范式。我们在最近的研究中发现，今天的人是低地人的后代。在这些受试者心脏和大脑葡萄糖代谢的试点体位发射断层扫描(PET)研究中，我们发现利用生物医学适应来维持每个器官的能量平衡，尽管他们的家环境强加和长期低氧。心脏数据显示，即使在隔夜禁食之后，基本能量需求也严重依赖葡萄糖。这暂时被解释为一种适应，服务于最大限度地增加单位氧气可获得的有用能量。有趣的是，在海平面上只生活了20天后，受试者部分地，甚至在一个案例中完全恢复了底物偏好的正常模式。大脑对葡萄糖的摄取水平处于正常范围的最高端，这可能表明至少有一些非氧气依赖的新陈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对人类物种具有普遍性。出于这个原因，我们建议将我们的研究扩大到包括那些预计在基因和个体上也能适应低氧的受试者，尼泊尔的夏尔巴人。

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.