Dual Regulatory Role of Polyamines in Adipogenesis.
J Biol Chem
; 290(45): 27384-27392, 2015 Nov 06.
Article
em En
| MEDLINE
| ID: mdl-26396188
ABSTRACT
Adipogenesis is a complex process, accompanied by a chain of interdependent events. Disruption of key events in this cascade may interfere with the correct formation of adipose tissue. Polyamines were demonstrated necessary for adipogenesis; however, the underlying mechanism by which they act has not been established. Here, we examined the effect of polyamine depletion on the differentiation of 3T3-L1 preadipocytes. Our results demonstrate that polyamines are required early in the adipogenic process. Polyamine depletion inhibited the second division of the mitotic clonal expansion (MCE), and inhibited the expression of PPARγ and C/EBPα, the master regulators of adipogenesis. However, it did not affect the expression of their transcriptional activator, C/EBPß. Additionally, polyamine depletion resulted in elevation of mRNA and protein levels of the stress-induced C/EBP homologous protein (CHOP), whose dominant negative function is known to inhibit C/EBPß DNA binding activity. Conditional knockdown of CHOP in polyamine-depleted preadipocytes restored PPARγ and C/EBPα expression, but failed to recover MCE and differentiation. Thus, our results suggest that the need for MCE in the adipogenic process is independent from the requirement for PPARγ and C/EBPα expression. We conclude that de novo synthesis of polyamines during adipogenesis is required for down-regulation of CHOP to allow C/EBPß activation, and for promoting MCE.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Poliaminas Biogênicas
/
Adipogenia
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article