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Article: Inhibitory effects of A-769662, a novel activator of AMP-activated protein kinase, on 3T3-L1 adipogenesis

TitleInhibitory effects of A-769662, a novel activator of AMP-activated protein kinase, on 3T3-L1 adipogenesis
Authors
Keywords3T3-l1 adipogenesis
A-769662
Acetyl-CoA carboxylase
AMP-activated protein kinase
Cell viability
Mitotic clonal expansion
Issue Date2009
PublisherPharmaceutical Society of Japan. The Journal's web site is located at http://bpb.pharm.or.jp/index.html
Citation
Biological And Pharmaceutical Bulletin, 2009, v. 32 n. 6, p. 993-998 How to Cite?
AbstractAMP-activated protein kinase (AMPK) is a central player in glucose and lipid metabolism while its role in adipocyte differentiation remains obscure. A-769662, a novel activator of AMPK, has been implicated to reduce body weight gain and decrease liver and plasma triglyceride levels via increasing fatty acid oxidation and reducing fatty acid synthesis in vivo. In this study, we examined the effects of A-769662 on adipocyte differentiation using 3T3-L1 cells. We found that A-769662 significantly inhibited 3T3-L1 differentiation via down-regulation of adipogenesis-related transcription factors and adipogenic markers. The inhibitory effect mainly occurred at the early phase of differentiation through inhibition of mitotic clonal expansion (MCE), which was essential for adipogenesis. A-769662 also decreased cell viability of differentiating and mature 3T3-L1 adipocytes. Moreover, treatment of differentiating 3T3-L1 cells with A-769662 resulted in AMPK over-activation, which led to an increased phosphorylation and inactivation of acetyl-CoA carboxylase (ACC), an important enzyme for the synthesis and usage of fatty acids. Taken together, these results suggest that A-769662 inhibits 3T3-L1 adipogenic differentiation in several ways and therefore may be a promising compound for the treatment of obesity. © 2009 Pharmaceutical Society of Japan.
Persistent Identifierhttp://hdl.handle.net/10722/59317
ISSN
2023 Impact Factor: 1.7
2023 SCImago Journal Rankings: 0.518
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhou, Yen_HK
dc.contributor.authorWang, Den_HK
dc.contributor.authorZhu, Qen_HK
dc.contributor.authorGao, Xen_HK
dc.contributor.authorYang, Sen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorWu, Den_HK
dc.date.accessioned2010-05-31T03:47:36Z-
dc.date.available2010-05-31T03:47:36Z-
dc.date.issued2009en_HK
dc.identifier.citationBiological And Pharmaceutical Bulletin, 2009, v. 32 n. 6, p. 993-998en_HK
dc.identifier.issn0918-6158en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59317-
dc.description.abstractAMP-activated protein kinase (AMPK) is a central player in glucose and lipid metabolism while its role in adipocyte differentiation remains obscure. A-769662, a novel activator of AMPK, has been implicated to reduce body weight gain and decrease liver and plasma triglyceride levels via increasing fatty acid oxidation and reducing fatty acid synthesis in vivo. In this study, we examined the effects of A-769662 on adipocyte differentiation using 3T3-L1 cells. We found that A-769662 significantly inhibited 3T3-L1 differentiation via down-regulation of adipogenesis-related transcription factors and adipogenic markers. The inhibitory effect mainly occurred at the early phase of differentiation through inhibition of mitotic clonal expansion (MCE), which was essential for adipogenesis. A-769662 also decreased cell viability of differentiating and mature 3T3-L1 adipocytes. Moreover, treatment of differentiating 3T3-L1 cells with A-769662 resulted in AMPK over-activation, which led to an increased phosphorylation and inactivation of acetyl-CoA carboxylase (ACC), an important enzyme for the synthesis and usage of fatty acids. Taken together, these results suggest that A-769662 inhibits 3T3-L1 adipogenic differentiation in several ways and therefore may be a promising compound for the treatment of obesity. © 2009 Pharmaceutical Society of Japan.en_HK
dc.languageengen_HK
dc.publisherPharmaceutical Society of Japan. The Journal's web site is located at http://bpb.pharm.or.jp/index.htmlen_HK
dc.relation.ispartofBiological and Pharmaceutical Bulletinen_HK
dc.subject3T3-l1 adipogenesis-
dc.subjectA-769662-
dc.subjectAcetyl-CoA carboxylase-
dc.subjectAMP-activated protein kinase-
dc.subjectCell viability-
dc.subjectMitotic clonal expansion-
dc.subject.mesh3T3-L1 Cellsen_HK
dc.subject.meshAMP-Activated Protein Kinases - metabolismen_HK
dc.subject.meshAcetyl-CoA Carboxylase - antagonists & inhibitorsen_HK
dc.subject.meshAdipocytes - cytology - drug effects - enzymology - metabolismen_HK
dc.subject.meshAdipogenesis - drug effects - geneticsen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCell Differentiation - drug effectsen_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshCell Survival - drug effectsen_HK
dc.subject.meshFatty Acids - metabolismen_HK
dc.subject.meshMiceen_HK
dc.subject.meshPyrones - pharmacologyen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshThiophenes - pharmacologyen_HK
dc.titleInhibitory effects of A-769662, a novel activator of AMP-activated protein kinase, on 3T3-L1 adipogenesisen_HK
dc.typeArticleen_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1248/bpb.32.993en_HK
dc.identifier.pmid19483304-
dc.identifier.scopuseid_2-s2.0-66549123846en_HK
dc.identifier.hkuros157978en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-66549123846&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume32en_HK
dc.identifier.issue6en_HK
dc.identifier.spage993en_HK
dc.identifier.epage998en_HK
dc.identifier.isiWOS:000266483500007-
dc.publisher.placeJapanen_HK
dc.identifier.scopusauthoridZhou, Y=25654258200en_HK
dc.identifier.scopusauthoridWang, D=14051219700en_HK
dc.identifier.scopusauthoridZhu, Q=54898305300en_HK
dc.identifier.scopusauthoridGao, X=26028577700en_HK
dc.identifier.scopusauthoridYang, S=7408519878en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridWu, D=7404297751en_HK
dc.identifier.issnl0918-6158-

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