10‐Hydroxy‐2‐decenoic acid, a unique medium‐chain fatty acid, activates 5'‐ AMP ‐activated protein kinase in L 6 myotubes and mice

Scope 10‐Hydroxy‐2‐decenoic acid (10 H 2 DA ) is one of the unique medium‐chain fatty acids ( MCFA s) specifically found in royal jelly. We hypothesize that 10 H 2 DA has multiple biological functions and may aid in 5′‐ AMP ‐activated protein kinase ( AMPK ) activation and affect the glucose transport system in skeletal muscle. Methods and results We examined whether various MCFA s present in royal jelly activated AMPK α. Treatment of L 6 myotubes with various MCFA s showed that 10 H 2 DA administration resulted in a significant increase in phosphorylated AMPK α. 10 H 2 DA activates AMPK independently of insulin and significantly increased glucose uptake into L 6 myotubes following translocation of glucose transporter 4 ( G lut4) to the plasma membrane ( PM ). The activation was induced by the upstream kinase C a 2+ /calmodulin‐dependent kinase kinase β, but was independent of changes in AMP : ATP ratio and the liver kinase B1 pathway. Oral administration of 10 H 2 DA significantly stimulated phosphorylation of AMPK and Glut4 translocation to the PM in mouse skeletal muscle. Conclusion These findings indicate that (i) 10 H 2 DA activates AMPK , and insulin independently enhances glucose uptake following translocation of G lut4 to PM , (ii) activation of AMPK α by 10 H 2 DA is mediated via extracellular C a 2+ ‐dependent C a 2+ /calmodulin‐dependent kinase kinase β, without alteration in the AMP : ATP ratio, and liver kinase B1 was not involved in the activation.