Interferon-alpha inhibits adipogenesis via regulation of JAK/STAT1 signaling.
Biochim Biophys Acta
; 1860(11 Pt A): 2416-2427, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27424923
ABSTRACT
BACKGROUND INFORMATION Adipose tissue regulates energy metabolism by means of adipocyte hypertrophy and/or the differentiation of pre-existing adipocytes. Excessive production of some cytokines in adipose tissue is known to be a negative regulator of adipocyte differentiation, and the resulting impaired adipogenesis contributes to disorders like insulin resistance. IFN-α is a key immunoregulatory cytokine in the development of type 1 diabetes, lipid disorders and insulin resistance; however, its effect on adipogenesis remains unknown. METHOD:
We examined the effect of IFN-α on adipocyte differentiation and its mechanisms. The effect of IFN-α on adipogenesis was evaluated by Western blotting, qRT-PCR, flow cytometric analysis and Oil Red O staining. We also investigated the role of STAT1 in adipogenesis using gene silencing analysis.RESULTS:
IFN-α inhibited the accumulation of lipid droplets and the expression of adipogenesis related genes. The inhibition of adipocyte differentiation by IFN-α occurred in the early stages of differentiation. IFN-α arrested the cell cycle at the G0/G1 phase and regulated the expression of CDK2 and p21. These results were confirmed in MEF cells. Treatment with IFN-α increased STAT1 phosphorylation, and STAT1 siRNA or inhibitor prevented IFN-α from inhibiting the expression of PPARγ and C/EBPα as well as cell cycle progression in 3T3-L1 cells.CONCLUSION:
We suggest that IFN-α inhibits adipocyte differentiation during the early stage of adipogenesis by regulating the expression of PPARγ and C/EBPα as well as the cell cycle through JAK/STAT1 signaling pathways. GENERALSIGNIFICANCE:
Our study provides new insights into possible mechanisms of the anti-adipogenetic effects of IFN-α.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Interferon-alfa
/
Fator de Transcrição STAT1
/
Adipogenia
/
Janus Quinases
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2016
Tipo de documento:
Article