Preventive effect of fermented whey protein mediated by Lactobacillus gasseri IM13 via the PI3K/AKT/FOXO pathway in muscle atrophy

J Dairy Sci. 2024 May;107(5):2606-2619. doi: 10.3168/jds.2023-24027. Epub 2023 Nov 16.

Abstract

This study investigated the preventive effects of whey protein fermented with Lactobacillus gasseri IM13 (F-WP) against dexamethasone (DEX)-induced muscle atrophy. C2C12 muscle cells were treated with F-WP followed by DEX treatment. Dexamethasone treatment inhibited myotube formation and the expression of myogenic regulatory factors; however, pretreatment with F-WP attenuated DEX-induced damage. The F-WP significantly activated the phosphorylation of the IGF-1/PI3K/AKT pathway and improved muscle homeostasis suppressed by DEX. Moreover, F-WP alleviated the phosphorylation of mTOR, S6K1, and 4E-BP1 and enhanced muscle protein synthesis. Muscle-specific ubiquitin ligases and autophagy lysosomes, which were activated by the dephosphorylation of FOXO3a by DEX treatment, were significantly attenuated by F-WP pretreatment of myotubes. For peptidomic analysis, F-WP was fractionated using preparative HPLC (prep-HPLC), and the AA sequences of 11 peptides were identified using MALDI-TOF/MS/MS. In conclusion, fermentation of whey protein by the specific probiotic strain IM13 produced bioactive peptides with high antioxidant and anti-sarcopenic-sarcopenic effects, which markedly enhanced myogenesis and muscle protein synthesis while diminishing muscle protein degradation compared with intact whey protein.

Keywords: Lactobacillus gasseri; fermentation; muscle atrophy; peptide; whey protein.

MeSH terms

  • Animals
  • Dexamethasone / pharmacology
  • Lactobacillus gasseri* / metabolism
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology
  • Muscle Proteins
  • Muscle, Skeletal* / metabolism
  • Muscular Atrophy* / chemically induced
  • Muscular Atrophy* / metabolism
  • Muscular Atrophy* / prevention & control
  • Muscular Atrophy* / veterinary
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Tandem Mass Spectrometry / veterinary
  • Whey Proteins / metabolism
  • Whey Proteins / pharmacology

Substances

  • Proto-Oncogene Proteins c-akt
  • Whey Proteins
  • Phosphatidylinositol 3-Kinases
  • Dexamethasone
  • Muscle Proteins