10-Hydroxy-2-Decenoic Acid, a Unique Medium-Chain Fatty
Acid, Activates 5'-AMP-Activated Protein Kinase in L6 Myotubes and Mice
Mol Nutr Food Res, 2013 Jun 10
SCOPE:
10-Hydroxy-2-decenoic acid (10H2DA) is one of the unique
medium-chain fatty acids (MCFAs) specifically found in royal jelly. We
hypothesize that 10H2DA 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 MCFAs present in royal jelly
activated AMPKα. Treatment of L6 myotubes with various MCFAs showed that 10H2DA
administration resulted in a significant increase in phosphorylated AMPKα.
10H2DA activates AMPK independently of insulin and significantly increased
glucose uptake into L6 myotubes following translocation of glucose transporter
4 (Glut4) to the plasma membrane (PM). The activation was induced by the
upstream kinase Ca2+ /calmodulin-dependent kinase kinase β, but was independent
of changes in AMP:ATP ratio and the liver kinase B1 pathway. Oral
administration of 10H2DA significantly stimulated phosphorylation of AMPK and
Glut4 translocation to the PM in mouse skeletal muscle.
CONCLUSION:
These findings indicate that (i) 10H2DA activates AMPK, and
insulin independently enhances glucose uptake following translocation of Glut4
to PM, (ii) activation of AMPKα by 10H2DA is mediated via extracellular Ca2+
-dependent Ca2+ /calmodulin-dependent kinase kinase β, without alteration in
the AMP:ATP ratio, and liver kinase B1 was not involved in the activation.
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