4-O-methylascochlorin suppresses differentiation of 3T3-L1 preadipocytes by inhibiting PPARγ expression through regulation of AMPK/mTOR signaling pathways.
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.
Department of Physical Therapy, Inje University, Gimhae, 621-749, Republic of Korea.
Mihyun
M
Kim
Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
Hyun-Ji
HJ
Cho
Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
Yun-Jeong
YJ
Jeong
Department of Biotechnology, Catholic University of Daegu, Gyeongsan 712-702, Republic of Korea.
Il-Kyung
IK
Chung
Magae Bioscience Institute, 49-4 Fujimidai, Tsukuba 300-1263, Japan.
Junji
J
Magae
Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea. Electronic address: ycchang@cu.ac.kr.
Young-Chae
YC
Chang
D041721:3T3-L1 Cells; D000263:Adenylate Kinase / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology*
D047495:PPAR gamma; D013729:Terpenes; C031515:4-O-methylascochlorin; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase
AMPK; Adipocyte; Differentiation; PPARγ; mTOR