美国加州大学旧金山分校Isha H. Jain课题组发现，急性和慢性缺氧时器官特异性燃料重构重新分配葡萄糖和脂肪酸的代谢。2023年3月7日出版的《细胞—代谢》杂志发表了这项成果。

研究人员报道了系统性缺氧如何重塑燃料代谢来优化整个身体的适应。适应缺氧的同时，血糖和脂肪也大大降低。使用体内燃料摄取和通量测量，研究人员发现在缺氧适应过程中，各器官对燃料的分配不同。急性期，大多数器官增加了葡萄糖的摄取，抑制了有氧葡萄糖的氧化，这与以前的体外研究一致。相反，棕色脂肪组织和骨骼肌成为“葡萄糖拯救者”，抑制葡萄糖吸收3-5倍。有趣的是，慢性缺氧产生了不同的模式：心脏越来越依赖葡萄糖的氧化，而出乎意料的是，大脑、肾脏和肝脏增加了脂肪酸的摄取和氧化。缺氧诱导的代谢可塑性对慢性代谢性疾病和急性缺氧性损伤具有治疗意义。

据介绍，缺氧可能是有害的。然而，慢性缺氧也与高海拔人群中代谢综合征和心血管疾病的发病率降低有关。以前，低氧燃料重塑主要是在永生细胞中被研究。

附：英文原文

Title: Organ-specific fuel rewiring in acute and chronic hypoxia redistributes glucose and fatty acid metabolism

Author: Ayush D. Midha, Yuyin Zhou, Bruno B. Queliconi, Alec M. Barrios, Augustinus G. Haribowo, Brandon T.L. Chew, Cyril O.Y. Fong, Joseph E. Blecha, Henry VanBrocklin, Youngho Seo, Isha H. Jain

Issue&Volume: 2023/03/07

Abstract: Oxygen deprivation can be detrimental. However, chronic hypoxia is also associatedwith decreased incidence of metabolic syndrome and cardiovascular disease in high-altitudepopulations. Previously, hypoxic fuel rewiring has primarily been studied in immortalizedcells. Here, we describe how systemic hypoxia rewires fuel metabolism to optimizewhole-body adaptation. Acclimatization to hypoxia coincided with dramatically lowerblood glucose and adiposity. Using in vivo fuel uptake and flux measurements, we found that organs partitioned fuels differentlyduring hypoxia adaption. Acutely, most organs increased glucose uptake and suppressedaerobic glucose oxidation, consistent with previous in vitro investigations. In contrast, brown adipose tissue and skeletal muscle became “glucosesavers,” suppressing glucose uptake by 3–5-fold. Interestingly, chronic hypoxia produceddistinct patterns: the heart relied increasingly on glucose oxidation, and unexpectedly,the brain, kidney, and liver increased fatty acid uptake and oxidation. Hypoxia-inducedmetabolic plasticity carries therapeutic implications for chronic metabolic diseasesand acute hypoxic injuries.

DOI: 10.1016/j.cmet.2023.02.007

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00043-8