Muscle Conditional Medium Reduces Intramuscular Adipocyte Differentiation and Lipid Accumulation through Regulating Insulin Signaling

Int J Mol Sci. 2017 Aug 20;18(8):1799. doi: 10.3390/ijms18081799.

Abstract

Due to the paracrine effects of skeletal muscle, the lipid metabolism of porcine intramuscular (i.m.) preadipocytes was different from that of subcutaneous (s.c.) preadipocytes. To investigate the development of i.m. preadipocytes in vivo, the s.c. preadipocytes were cultured with muscle conditional cultured medium (MCM) for approximating extracellular micro-environment of the i.m. preadipocytes. Insulin signaling plays a fundamental role in porcine adipocyte differentiation. The expression levels of insulin receptor (INSR) and insulin-like growth factor 1 receptor (IGF-1R) in i.m. Preadipocytes were higher than that in s.c. preadipocytes. The effects of MCM on adipocyte differentiation, lipid metabolism and insulin signaling transdution were verified. MCM induced the apoptosis of s.c. preadipocytes but not of s.c. adipocytes. Moreover, MCM inhibited adipocyte differentiation at pre-differentiation and early stages of differentiation, while the expression levels of INSR and IGF-1R were increased. Furthermore, MCM treatment increased adipocyte lipolysis and fatty acid oxidation through induction of genes involved in lipolysis, thermogenesis, and fatty acid oxidation in mitochondria. Consistent with the above, treatment of s.c. adipocytes with MCM upregulated mitochondrial biogenesis. Taken together, MCM can approximate the muscle micro-environment and reduce intramuscular adipocyte differentiation and lipid accumulation via regulating insulin signaling.

Keywords: adipogenesis; extracellular micro-environment; insulin receptor; insulin-like growth factor 1 receptor; intramuscular preadipocytes; porcine.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Adipogenesis / genetics
  • Animals
  • Apoptosis / drug effects
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Cell Proliferation / drug effects
  • Cellular Microenvironment / drug effects
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology*
  • Insulin / genetics
  • Insulin / metabolism
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics*
  • Mice
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Organelle Biogenesis
  • Paracrine Communication / genetics
  • Receptor, IGF Type 1 / genetics
  • Receptor, Insulin / genetics
  • Signal Transduction / drug effects
  • Swine

Substances

  • Culture Media, Conditioned
  • Insulin
  • Receptor, IGF Type 1
  • Receptor, Insulin
  • insulin receptor-related receptor