Porcine peroxisome proliferator-activated receptor gamma induces transdifferentiation of myocytes into adipocytes.
Peroxisome proliferator-activated receptor gamma2 (PPARgamma) is a nuclear transcription factor that regulates adipocyte differentiation and lipogenic genes during adipogenesis. The activity of rodent PPARgamma is regulated by phosphorylation of serine 112. The current experiment was designed to study the ability of porcine PPARgamma to stimulate transdifferentiation of myoblasts to adipocytes by overexpressing wild-type PPARgamma or mutated PPARgamma (serine 112 was mutated to alanine) in mouse myoblast cells. The expression of adipogenic marker genes (adipocyte fatty acid binding protein, lipoprotein lipase, and glycerol-3 phosphate dehydrogenase) in cells stably expressing mutated porcine PPARgamma was greater than in cells with wild-type PPARgamma, indicating that the mutated PPARgamma has greater adipogenic capability than the wild-type PPARgamma. Under treatment with a ligand, both wild-type and mutant porcine PPARgamma-expressing C2C12 myoblasts differentiated into adipocytes in 10 d. The expression of myogenic marker genes (myogenin, myogenic regulatory factor-4) was suppressed in cells transfected with the mutated PPARgamma or wild-type PPARgamma. Moreover, wild-type and mutant PPARgamma were able to inhibit myogenesis without addition of a ligand. Our results suggest that porcine wild-type PPARgamma and mutated PPARgamma can both convert myoblast cells into adipocytes, and also that the ability to transdifferentiate was greater in cells containing the mutated PPARgamma than in cells containing the wild-type PPARgamma. Therefore, the existence of serine 112 in PPARgamma may have a role in regulating adipocyte differentiation.
Yu
Y H
YH
Department of Animal Science and Technology, National Taiwan University, Taipei 106, Taiwan.
Liu
B H
BH
Mersmann
H J
HJ
Ding
S T
ST
D017667:Adipocytes / Q000166:cytology* / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D054338:Cell Transdifferentiation; D003470:Culture Media; D017931:DNA Primers / Q000737:chemistry; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008055:Lipids / Q000032:analysis; D032342:Muscle Cells / Q000166:cytology* / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009154:Mutation / Q000502:physiology; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D047495:PPAR gamma / Q000502:physiology*; D000077154:Rosiglitazone; D013552:Swine / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology
D003470:Culture Media; D017931:DNA Primers; D007004:Hypoglycemic Agents; D008055:Lipids; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone