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

Ayush D Midha; Yuyin Zhou; Bruno B QueliconiAlec M BarriosAugustinus G HaribowoBrandon T L ChewCyril O Y FongJoseph E BlechaHenry VanBrocklinYoungho SeoIsha H Jain

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

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

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Oxygen deprivation can be detrimental. However, chronic hypoxia is also associated with decreased incidence of metabolic syndrome and cardiovascular disease in high-altitude populations. Previously, hypoxic fuel rewiring has primarily been studied in immortalized cells. Here, we describe how systemic hypoxia rewires fuel metabolism to optimize whole-body adaptation. Acclimatization to hypoxia coincided with dramatically lower blood glucose and adiposity. Using in vivo fuel uptake and flux measurements, we found that organs partitioned fuels differently during hypoxia adaption. Acutely, most organs increased glucose uptake and suppressed aerobic glucose oxidation, consistent with previous in vitro investigations. In contrast, brown adipose tissue and skeletal muscle became "glucose savers," suppressing glucose uptake by 3-5-fold. Interestingly, chronic hypoxia produced distinct patterns: the heart relied increasingly on glucose oxidation, and unexpectedly, the brain, kidney, and liver increased fatty acid uptake and oxidation. Hypoxia-induced metabolic plasticity carries therapeutic implications for chronic metabolic diseases and acute hypoxic injuries.

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《Cell metabolism》 |2023年第3期|504-516|共13页
作者
Ayush D Midha; Yuyin Zhou; Bruno B QueliconiAlec M BarriosAugustinus G HaribowoBrandon T L ChewCyril O Y FongJoseph E BlechaHenry VanBrocklinYoungho SeoIsha H Jain;
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作者单位

Gladstone Institutes, San Francisco, CA 94158, USA;

Department of Biochemistry and Biophysics;

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正文语种英语
中图分类内分泌腺疾病及代谢病;
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PET scan; TCA cycle; fatty acid metabolism; fuel rewiring; fuel uptake; glucose metabolism; hypoxia; isotope tracing; organ-specific metabolism;

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

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