4-O-methylascochlorin suppresses differentiation of 3T3-L1 preadipocytes by inhibiting PPARγ expression through regulation of AMPK/mTOR signaling pathways.
Arch Biochem Biophys
; 583: 79-86, 2015 Oct 01.
Article
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| MEDLINE
| ID: mdl-26271443
ABSTRACT
Obesity increases the risk of developing many chronic diseases, including type 2 diabetes and certain cancers, and is thereby associated with premature death. The present study was conducted to identify the inhibitory effect of the ascochlorin derivative 4-O-methylascochlorin (MAC) on the differentiation of 3T3-L1 preadipocytes. MAC suppressed the differentiation of 3T3-L1 preadipocytes and inhibited the expression of adipocyte differentiation marker genes, FABP4, PPARγ and C/EBPα. In addition, we found that the inhibitory effects of MAC on differentiation of 3T3-L1 preadipocytes were caused by suppression of mTORC1 via inhibition of mTOR/p70S6K/4E-BP1 phosphorylation and activation of Raptor phosphorylation. MAC also regulated the PPARγ expression and the mTORC1 activation by increasing AMPK phosphorylation and inhibiting PI3K/Akt, which suggest that MAC suppresses the differentiation of 3T3-L1 adipocytes by regulating the AMPK- and PI3K-mTOR-PPARγ signaling pathways. Furthermore, animal model results showed that the phosphorylation of AMPK was enhanced in the liver of C57BL/6 mice intraperitoneally injected with MAC. These results indicate that MAC could be a therapeutic agent for obesity involving PPARγ and AMPK.
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1
Banco de datos:
MEDLINE
Asunto principal:
Terpenos
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Transducción de Señal
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Diferenciación Celular
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Adenilato Quinasa
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Adipocitos
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PPAR gamma
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Serina-Treonina Quinasas TOR
Límite:
Animals
Idioma:
En
Revista:
Arch Biochem Biophys
Año:
2015
Tipo del documento:
Article