Beta-hydroxy beta-methyl butyrate decreases muscle protein degradation via increased Akt/FoxO3a signaling and mitochondrial biogenesis in weanling piglets after lipopolysaccharide challenge

Food Funct. 2019 Aug 1;10(8):5152-5165. doi: 10.1039/c9fo00769e. Epub 2019 Aug 2.

Abstract

The aim of this study was to investigate the effects of dietary β-hydroxy-β-methylbutyrate (HMB) on lipopolysaccharide (LPS)-induced muscle atrophy and to investigate the mechanisms involved. Sixty pigs (21 ± 2 days old, 5.86 ± 0.18 kg body weight) were used in a 2 × 3 factorial design and the main factors included diet (0, 0.60%, or 1.20% HMB) and immunological challenge (LPS or saline). After 15 d of treatment with LPS and/or HMB, growth performance, blood parameters, and muscle protein degradation rate were measured. The results showed that in LPS-injected pigs, 0.60% HMB supplementation increased the average daily gain and average daily feed intake and decreased the feed : gain ratio (P < 0.05), with a concurrent increase of lean percentage. Moreover, 0.60% HMB supplementation decreased the serum concentrations of blood urea nitrogen, IL-1β, and TNF-α and the rate of protein degradation as well as cell apoptosis in selected muscles (P < 0.05). In addition, dietary HMB supplementation (0.60%) regulated the expression of genes involved in mitochondrial biogenesis and increased the phosphorylation of Akt and Forkhead Box O3a (FoxO3a) in selected muscles, accompanied by decreased protein expression of muscle RING finger 1 and muscle atrophy F-box. These results indicate that HMB may exert protective effects against LPS-induced muscle atrophy by normalizing the Akt/FoxO3a axis that regulates ubiquitin proteolysis and by improving mitochondrial biogenesis.

MeSH terms

  • Animal Feed / analysis
  • Animals
  • Female
  • Forkhead Box Protein O3 / genetics
  • Forkhead Box Protein O3 / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / adverse effects
  • Male
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Muscle Proteins / metabolism*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Muscular Atrophy / chemically induced
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / prevention & control
  • Muscular Atrophy / veterinary*
  • Organelle Biogenesis
  • Proteolysis / drug effects
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Swine
  • Swine Diseases / chemically induced
  • Swine Diseases / genetics
  • Swine Diseases / metabolism
  • Swine Diseases / prevention & control*
  • Valerates / administration & dosage*

Substances

  • Forkhead Box Protein O3
  • Interleukin-1beta
  • Lipopolysaccharides
  • Muscle Proteins
  • Valerates
  • beta-hydroxyisovaleric acid
  • Proto-Oncogene Proteins c-akt