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

• Published in: Cell metabolism Vol. 27; no. 5; pp. 1111 - 1120.e3
• Main Authors: Stanford, Kristin I., Lynes, Matthew D., Takahashi, Hirokazu, Baer, Lisa A., Arts, Peter J., May, Francis J., Lehnig, Adam C., Middelbeek, Roeland J.W., Richard, Jeffrey J., So, Kawai, Chen, Emily Y., Gao, Fei, Narain, Niven R., Distefano, Giovanna, Shettigar, Vikram K., Hirshman, Michael F., Ziolo, Mark T., Kiebish, Michael A., Tseng, Yu-Hua, Coen, Paul M., Goodyear, Laurie J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2018
• Subjects: Adipose Tissue, Brown - metabolism; Adult; Aged; Aged, 80 and over; Animals; brown adipose tissue; Cell Line; Cohort Studies; Cold Temperature; Exercise; Female; Healthy Volunteers; Humans; Lipid Metabolism - drug effects; lipokines; Male; metabolism; Mice; Mice, Inbred C57BL; Middle Aged; Muscle, Skeletal - metabolism; Oleic Acids - metabolism; Oxygen - metabolism; Oxygen Consumption - drug effects; Physical Conditioning, Animal; lipokines; exercise; metabolism; brown adipose tissue
• ISSN: 1550-4131; 1932-7420
• 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.
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•Exercise increases circulating levels of the lipokine 12,13-diHOME in humans and mice•iBAT is the tissue source for the exercise-stimulated increase in 12,13-diHOME in mice•12,13-diHOME increases fatty acid uptake and oxidation in skeletal muscle of mice
Using an MS/MSALL lipidomics platform, Stanford et al. identify 12,13-diHOME as an exercised-induced lipokine in male, female, young, and old human subjects. Murine experiments show that BAT is the tissue source of exercise-induced increases in circulating 12,13-diHOME, and that this lipokine increases fatty acid uptake in skeletal muscle in vivo.