BMP Inhibition with dorsomorphin limits adipogenic potential of preadipocytes.
Previous studies revealed that bone morphogenetic protein (BMP) induces commitment to the adipocyte lineage in pluripotent stem cells. The present study explored the role of endogenous BMP activity in 3T3-L1 preadipocytes. The expression of phospho-Smad1/5/8 was monitored because BMP transmits its signal through Smad1/5/8 phosphorylation. Phosphorylated Smad1/5/8 was higher in proliferating preadipocytes, and lower in differentiating adipocytes after removing differentiation inducers. Reporter assays revealed that dorsomorphin predominantly inhibits the BMP pathway but not the structurally related TGF-beta/activin pathway. The addition of dorsomorphin to the culture medium prior to treatment with differentiation inducers impaired lipid accumulation in 3T3-L1 cells. The present study indicated that activation of BMP signaling in preadipocytes is required for these cells to initiate the adipogenic program.
Suenaga
Masashi
M
Division of Applied Biosciences, Kyoto University Graduate School of Agriculture, Kitashirakawa Oiwakecho, Kyoto 606-8502, Japan.
Matsui
Tohru
T
Funaba
Masayuki
M
D041721:3T3-L1 Cells / Q000166:cytology / Q000187:drug effects; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D011720:Pyrazoles; D011743:Pyrimidines; C516138:dorsomorphin