Abstract
Cold and hypoxia are critical drivers of adaptation to high altitudes. Organisms at high altitudes have adapted to maximize the efficiency of oxygen utilization and are less prone to obesity and diabetes than those at low altitudes. Brown adipose tissue (BAT) dissipates energy in the form of heat in both humans and rodents; it also serves to regulate metabolism to curb obesity. However, the role of BAT in high-altitude populations is poorly understood. Serum exosomes can be easily obtained, enabling the study of BAT functions and identification of biomarkers in serum exosomes, both of which contribute to understanding the role of BAT in high-altitude populations. 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography integrated with computed tomography (PET/CT) is the gold standard for studying BAT in human adults. Here, we studied BAT in healthy high-altitude populations via PET/CT and serum exosomal microRNAs (miRNAs). The observations were validated in mouse tissues and demonstrated that high-altitude hypoxia activated BAT through attenuated white adipose tissue (WAT) secreted exosomal miR-210/92a, which enhanced the FGFR-1 expression in BAT.
Highlights
Hypoxia exerts profound systemic effects on metabolism
We used positron emission tomography integrated with computed tomography (PET/CT) scanning in high-altitude populations to clarify the global Brown adipose tissue (BAT) amount
The exosomal miRNAs originated from white adipose tissue (WAT) and activated BAT through enhanced the FGFR-1, which demonstrated that WAT plays the leading role in the high BAT activity under chronic hypoxia exposure
Summary
Hypoxia exerts profound systemic effects on metabolism. It is implicated in a broad spectrum of metabolic disorders, such as obesity and d iabetes[1]. These mechanisms include enhanced oxygen delivery, efficient consumption of limited oxygen through increased RBC production[5,6] and reprogramming of both g lobal[7] and tissue-specific metabolic processes, such as decreases in muscle oxidative phosphorylation and fatty acid oxidation but increases in cellular glycolysis and mitochondrial coupling efficiency[8,9] These adaptations have enabled populations dwelling long-term at high altitudes to survive. Increased BAT activity is associated with the enhanced heat generation and energy consumption, which in turn confers beneficial effects on adipose development, glucose metabolism and against obesity. Both pharmacological and physiological stimulation can be applied in preclinical approaches to promote BAT activity in human and rodent models. The exosomal miRNAs originated from WAT and activated BAT through enhanced the FGFR-1, which demonstrated that WAT plays the leading role in the high BAT activity under chronic hypoxia exposure
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