Hypoxia inhibits adipocyte differentiation in a HDAC-independent manner.
Oxygen is the most important factor for the appropriate regulation of multiple energy homeostasis and cell differentiation. Although hypoxia-induced signaling cascades have been intensively studied, the molecular mechanism by which hypoxic signals suppress adipocyte differentiation is unclear. Here, we demonstrated that repression of adipocyte differentiation by hypoxia and HIF1alpha- or Stra13-overexpression was not associated with HDACs. Furthermore, HDACs did not affect inhibitory effect of Stra13 on PPARgamma promoter activity, although the hypoxia-induced suppression of adipogenesis was accompanied with reduced acetylation of histone H3 and H4 at the PPARgamma promoter. Instead, we revealed that hypoxic circumstances biphasically activated AMPK and concomitantly blocked clonal expansion of preadipocytes, which is an indispensable step for early phase of adipocyte differentiation. Taken together, these results suggest that hypoxic condition attenuates adipocyte differentiation by inhibition of PPARgamma expression in a HDAC-independent manner and by activation of AMPK which impairs clonal expansion phase.
Kim
Kang Ho
KH
Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Song
Min Jeong
MJ
Chung
Jieun
J
Park
Hyunsung
H
Kim
Jae Bum
JB
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases; D017667:Adipocytes / Q000166:cytology* / Q000502:physiology*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000502:physiology; D015687:Cell Hypoxia; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D055372:AMP-Activated Protein Kinases; D051792:Basic Helix-Loop-Helix Proteins; D006655:Histone Deacetylases; D006657:Histones; D018398:Homeodomain Proteins; D009097:Multienzyme Complexes; D047495:PPAR gamma; D017346:Protein Serine-Threonine Kinases; C491539:Bhlhe40 protein, mouse