High glucose induces differentiation and adipogenesis in porcine muscle satellite cells via mTOR.
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.
Yue
Tao
T
State Key Laboratory of Animal Nutrition, College of Animal Science & Technology, China Agricultural University, Beijing 100193, China.
Yin
Jingdong
J
Li
Fengna
F
Li
Defa
D
Du
Min
M
D050156:Adipogenesis; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013552:Swine; D058570:TOR Serine-Threonine Kinases
D022763:CCAAT-Enhancer-Binding Protein-alpha; D047908:Intracellular Signaling Peptides and Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D064429:Fatty Acid Synthases; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D005947:Glucose