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Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Hypoxia inhibits adipocyte differentiation in a HDAC-independent manner
Kang Ho Kim1, Min Jeong Song, Jieun Chung
1Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Abstract:
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.
Insights
Hypoxia suppresses adipocyte differentiation by inhibiting PPARgamma expression independently of HDACs. It also activates AMPK, impairing preadipocyte clonal expansion, a key step in fat cell development.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolism
Background:
- Oxygen levels critically regulate energy homeostasis and cell differentiation.
- While hypoxia signaling is studied, its precise mechanism in suppressing adipocyte differentiation remains unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms by which hypoxia and related factors inhibit adipocyte differentiation.
- To investigate the roles of HDACs, PPARgamma, and AMPK in hypoxia-induced suppression of adipogenesis.
Main Methods:
- Overexpression of HIF1alpha and Stra13 to study hypoxia effects.
- Analysis of histone acetylation at the PPARgamma promoter.
- Assessment of AMPK activation and its impact on preadipocyte clonal expansion.
Main Results:
- Hypoxia and HIF1alpha/Stra13 overexpression suppressed adipocyte differentiation independently of HDACs.
- Hypoxia reduced histone H3/H4 acetylation at the PPARgamma promoter but HDACs did not mediate this effect.
- Hypoxic conditions biphasically activated AMPK and blocked preadipocyte clonal expansion.
Conclusions:
- Hypoxia attenuates adipocyte differentiation via HDAC-independent inhibition of PPARgamma expression.
- Activated AMPK under hypoxia impairs the clonal expansion phase of adipocyte differentiation.
