title: Octanoic acid promotes branched-chain amino acid catabolisms via the inhibition of hepatic branched-chain alpha-keto acid dehydrogenase kinase in rats.
abstract: OBJECTIVE
  It has been reported that administration of octanoic acid, one of medium-chain fatty acids (MCFAs), promoted leucine oxidation in vitro and in vivo, but it remained unclear how octanoic acid stimulated leucine oxidation. Therefore, the aim of this study was to elucidate the mechanism that octanoic acid facilitates branched-chain amino acid (BCAA) catabolism.
  
  
  METHODS
  In in vivo experiments, male rats were orally administered MCFAs as free fatty acids or triacylglycerol (trioctanoin), and then activities of hepatic branched-chain α-ketoacid dehydrogenase (BCKDH) complex (BCKDC) and BCKDH kinase (BDK) and alterations in the concentration of blood components were analyzed. In in vitro experiments, purified BCKDC associated with BDK (BCKDH-BDK complex) was reacted with various concentrations of hexanoic, octanoic, and decanoic acids.
  
  
  RESULTS
  Oral administration of trioctanoin in rats activated hepatic BCKDC via down-regulation of BDK activity in association with a decrease in plasma BCAA concentration and an increase in serum ketone body concentration. In vitro experiments using purified BCKDH-BDK complex showed that MCFAs (hexanoic, octanoic, and decanoic acids) inhibited BDK activity and that this inhibition was higher in hexanoic and octanoic acids than in decanoic acid. Oral administration of octanoic acid, but not decanoic acid, in rats activated hepatic BCKDC via down-regulation of BDK activity by decreasing the amount of BDK bound to the complex. The serum ketone body level was elevated by both administration of octanoic acid and decanoic acid.
  
  
  CONCLUSIONS
  These results suggest that octanoic acid promotes BCAA catabolism in vivo by activation of BCKDC via decreasing the bound form of BDK.
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kadota
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Takanari
authors.initials: T
authors.lastname: Toyoda
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hayashi-Kato
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kitaura
authors.affiliation: Department of Applied Molecular Biosciences, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan. Electronic address: shimo@agr.nagoya-u.ac.jp.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Shimomura
mesh_terms: D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D003652:Decanoic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007657:Ketone Bodies / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood / Q000494:pharmacology
chemical_list: D000597:Amino Acids, Branched-Chain; D002210:Caprylates; D003652:Decanoic Acids; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D014280:Triglycerides; C003637:tricaprylin; D042942:3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); C031492:octanoic acid
keywords: Branched-chain amino acid; Branched-chain α-ketoacid dehydrogenase complex; Branched-chain α-ketoacid dehydrogenase kinase; Medium-chain fatty acids; Trioctanoin