α-Ketoisocaproate and β-hydroxy-β-methyl butyrate regulate fatty acid composition and lipid metabolism in skeletal muscle of growing pigs

J Anim Physiol Anim Nutr (Berl). 2019 May;103(3):846-857. doi: 10.1111/jpn.13077. Epub 2019 Feb 18.

Abstract

Objectives: This study aims to investigate the effects and roles of excess leucine (Leu) versus its metabolites α-ketoisocaproate (KIC) and β-hydroxy-β-methyl butyrate (HMB) on fatty acid composition and lipid metabolism in skeletal muscle of growing pigs.

Methods and results: Thirty-two pigs with a similar initial weight (9.55 ± 0.19 kg) were fed one of the four diets (basal diet, L-Leu, KIC-Ca and HMB-Ca) for 45 days. Results indicated that dietary treatments did not affect the intramuscular fat (IMF) content (p > 0.05), but differently influenced the fatty acid composition of longissimus dorsi muscle (LM) and soleus muscle (SM). In particular, the proportion of N3 PUFA specifically in LM was significantly decreased in the Leu group and increased in both KIC and HMB group relative to the basal diet group (p < 0.05). Furthermore, pigs fed KIC-supplemented diets exhibited decreased expression of FATP-1, ACC, ATGL, C/EBPα, PPARγ and SREBP-1c in LM and increased expression of FATP-1, FAT/CD36, ATGL and M-CPT-1 in SM relative to the basal diet control (p < 0.05).

Conclusions: These findings indicated that doubling dietary Leu content decreased the percentage of N3 PUFA mainly in glycolytic skeletal muscle, whereas KIC and HMB improved muscular fatty acid composition and altered lipid metabolism in skeletal muscle of growing pigs. The mechanism of action of KIC might be related to the TFs, and the mechanism of action of HMB might be associated with the AMPK-mTOR signalling pathway.

Keywords: growing pigs; lipid metabolism; skeletal muscle; α-Ketoisocaproate; β-hydroxy-β-methyl butyrate.

Publication types

  • Clinical Trial, Veterinary

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • Animal Feed / analysis
  • Animal Nutritional Physiological Phenomena
  • Animals
  • Diet / veterinary
  • Fatty Acids / metabolism*
  • Gene Expression Regulation / drug effects
  • Keto Acids / metabolism
  • Keto Acids / pharmacology*
  • Leucine / administration & dosage
  • Leucine / metabolism
  • Leucine / pharmacology*
  • Lipid Metabolism / drug effects
  • Muscle, Skeletal / drug effects*
  • RNA, Messenger
  • Random Allocation
  • Swine / growth & development*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription Factors
  • Valerates / metabolism
  • Valerates / pharmacology*

Substances

  • Fatty Acids
  • Keto Acids
  • RNA, Messenger
  • Transcription Factors
  • Valerates
  • beta-hydroxyisovaleric acid
  • alpha-ketoisocaproic acid
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Leucine