Adipose-derived exosomal miR-210/92a cluster inhibits adipose browning via the FGFR-1 signaling pathway in high-altitude hypoxia

Sci Rep. 2020 Sep 1;10(1):14390. doi: 10.1038/s41598-020-71345-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / metabolism*
  • Adult
  • Altitude Sickness / metabolism*
  • Animals
  • Exosomes / metabolism*
  • Female
  • Fluorodeoxyglucose F18 / metabolism
  • Healthy Volunteers
  • Humans
  • Hypoxia / metabolism*
  • Maillard Reaction*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Positron Emission Tomography Computed Tomography
  • Radiopharmaceuticals / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / metabolism*
  • Signal Transduction

Substances

  • MIRN210 microRNA, human
  • MIRN210 microRNA, mouse
  • MicroRNAs
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • FGFR1 protein, human
  • Fgfr1 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 1