High glucose induces differentiation and adipogenesis in porcine muscle satellite cells via mTOR

BMB Rep. 2010 Feb;43(2):140-5. doi: 10.5483/bmbrep.2010.43.2.140.

Abstract

The present study investigated whether the mammalian target of rapamycin (mTOR) signal pathway is involved in the regulation of high glucose-induced intramuscular adipogenesis in porcine muscle satellite cells. High glucose (25 mM) dramatically increased intracellular lipid accumulation in cells during the 10-day adipogenic differentiation period. The expressions of CCAAT/enhancer binding protein-alpha (C/EBP-alpha) and fatty acid synthase (FAS) protein were gradually enhanced during the 10-day duration while mTOR phosphorylation and sterol-regulatory-element-binding protein (SREBP)-1c protein were induced on day 4. Moreover, inhibition of mTOR activity by rapamycin resulted in a reduction of SREBP-1c protein expression and adipogenesis in cells. Collectively, our findings suggest that the adipogenic differentiation of porcine muscle satellite cells and a succeeding extensive adipogenesis, which is triggered by high glucose, is initiated by the mTOR signal pathway through the activation of SREBP-1c protein. This process is previously uncharacterized and suggests a cellular mechanism may be involved in ectopic lipid deposition in skeletal muscle during type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis*
  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Fatty Acid Synthases / genetics
  • Fatty Acid Synthases / metabolism
  • Glucose / pharmacology*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Satellite Cells, Skeletal Muscle / cytology*
  • Signal Transduction
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Swine
  • TOR Serine-Threonine Kinases

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • Intracellular Signaling Peptides and Proteins
  • Sterol Regulatory Element Binding Protein 1
  • Fatty Acid Synthases
  • TOR Serine-Threonine Kinases
  • Protein-Serine-Threonine Kinases
  • Glucose