title: 10-Hydroxy-2-decenoic acid, a unique medium-chain fatty acid, activates 5'-AMP-activated protein kinase in L6 myotubes and mice.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi, Japan.
authors.forename: Masathito
authors.initials: M
authors.lastname: Takikawa
authors.forename: Aya
authors.initials: A
authors.lastname: Kumagai
authors.forename: Harumi
authors.initials: H
authors.lastname: Hirata
authors.forename: Minoru
authors.initials: M
authors.lastname: Soga
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Manabu
authors.initials: M
authors.lastname: Ueda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ashida
authors.forename: Takanori
authors.initials: T
authors.lastname: Tsuda
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005227:Fatty Acids / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D000099219:Royal Jelly
chemical_list: D055372:AMP-Activated Protein Kinases; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005947:Glucose; D051275:Glucose Transporter Type 4; D007328:Insulin; D000099219:Royal Jelly; C495694:Slc2a4 protein, rat; C055543:10-hydroxy-2-decenoic acid; C517701:Camkk1 protein, rat
keywords: 10-Hydroxy-2-decenoic acid; 5'-AMP-activated protein kinase; Ca2+/calmodulin-dependent kinase kinaseβ/Glucose transporter 4; Royal jelly