Exercise has many health benefits; however, the underlying mechanisms are largely unknown. Now, new research by Kristin Stanford, Laurie Goodyear and colleagues shows that exercise increases circulating levels of 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in humans and mice. This lipokine (a class of lipids released from adipose tissue that act as signalling molecules to influence metabolism) causes skeletal muscles to increase fatty acid oxidation and uptake. The study also showed that brown adipose tissue (BAT) is the source of 12,13-diHOME in mice following exercise.

Whether exercise can regulate lipokine levels was unknown, which prompted the researchers to undertake human and mouse model studies to investigate this issue. Stanford, Goodyear and co-workers recruited 39 healthy young and old, male and female volunteers with different activity levels (from sedentary to active lifestyles). Lipidomics analyses were performed on blood samples from volunteers taken before and after moderately intense exercise. The researchers showed that regardless of sex, age or activity levels, acute exercise substantially increased plasma levels of 12,13-diHOME.

Next, the authors replicated the human study in a mouse model and showed that mice also had elevated levels of 12,13-diHOME after exercise. As previous studies suggested that BAT is a source of 12,13-diHOME, the researchers surgically removed the intrascapular BAT in mice. The exercise-induced increase of 12,13-diHOME was blunted in these mice compared with mice that had sham surgery, which confirms that BAT is a source of 12,13-diHOME.

Finally, the researchers injected mice with a fatty acid and either 12,13-diHOME or a vehicle control. Skeletal muscle uptake of fatty acid was increased in mice that received 12,13-diHOME compared with those that received the control. In addition, cultured mouse muscle fibres incubated with 12,13-diHOME in vitro showed increased mitochondrial respiration.

“Here we see a new function for BAT with exercise, talking to the skeletal muscle to increase metabolism,” concludes Goodyear.