Oleanolic acid alleviates obesity-induced skeletal muscle atrophy via the PI3K/Akt signaling pathway

FEBS Open Bio. 2024 Apr;14(4):584-597. doi: 10.1002/2211-5463.13780. Epub 2024 Feb 17.

Abstract

Oleanolic acid (OA) is a pentacyclic triterpene with reported protective effects against various diseases, including diabetes, hepatitis, and different cancers. However, the effects of OA on obesity-induced muscle atrophy remain largely unknown. This study investigated the effects of OA on skeletal muscle production and proliferation of C2C12 cells. We report that OA significantly increased skeletal muscle mass and improved glucose intolerance and insulin resistance. OA inhibited dexamethasone (Dex)-induced muscle atrophy in C2C12 myoblasts by regulating the PI3K/Akt signaling pathway. In addition, it also inhibited expression of MuRF1 and Atrogin1 genes in skeletal muscle of obese mice suffering from muscle atrophy, and increased the activation of PI3K and Akt, thereby promoting protein synthesis, and eventually alleviating muscle atrophy. Taken together, these findings suggest OA may have potential for the prevention and treatment of muscle atrophy.

Keywords: PI3K/Akt signaling pathways; dexamethasone; muscle atrophy; obesity; oleanolic acid.

MeSH terms

  • Animals
  • Mice
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Atrophy* / chemically induced
  • Muscular Atrophy* / drug therapy
  • Muscular Atrophy* / metabolism
  • Obesity / complications
  • Obesity / drug therapy
  • Obesity / metabolism
  • Oleanolic Acid* / metabolism
  • Oleanolic Acid* / pharmacology
  • Oleanolic Acid* / therapeutic use
  • Phosphatidylinositol 3-Kinases / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction

Substances

  • Oleanolic Acid
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt