12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake

Cell Metab. 2018 May 1;27(5):1111-1120.e3. doi: 10.1016/j.cmet.2018.03.020.


Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects. In mice, both a single bout of exercise and exercise training increased circulating 12,13-diHOME and surgical removal of brown adipose tissue (BAT) negated the increase in 12,13-diHOME, suggesting that BAT is the tissue source for exercise-stimulated 12,13-diHOME. Acute 12,13-diHOME treatment of mice in vivo increased skeletal muscle fatty acid uptake and oxidation, but not glucose uptake. These data reveal that lipokines are novel exercise-stimulated circulating factors that may contribute to the metabolic changes that occur with physical exercise.

Keywords: brown adipose tissue; exercise; lipokines; metabolism.

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Line
  • Cohort Studies
  • Cold Temperature
  • Exercise*
  • Female
  • Healthy Volunteers
  • Humans
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Muscle, Skeletal / metabolism*
  • Oleic Acids / metabolism*
  • Oxygen / metabolism*
  • Oxygen Consumption / drug effects
  • Physical Conditioning, Animal


  • 12,13-dihydroxyoctadecenoic acid
  • Oleic Acids
  • Oxygen