title: Suppression of Adipocyte Differentiation by Foenumoside B from Lysimachia foenum-graecum Is Mediated by PPARγ Antagonism.
abstract: Lysimachia foenum-graecum extract (LFE) and its active component foenumoside B (FSB) have been shown to inhibit adipocyte differentiation, but their mechanisms were poorly defined. Here, we investigated the molecular mechanisms responsible for their anti-adipogenic effects. Both LFE and FSB inhibited the differentiation of 3T3-L1 preadipocytes induced by peroxisome proliferator-activated receptor-γ (PPARγ) agonists, accompanied by reductions in the expressions of the lipogenic genes aP2, CD36, and FAS. Moreover, LFE and FSB inhibited PPARγ transactivation activity with IC50s of 22.5 μg/ml and 7.63 μg/ml, respectively, and showed selectivity against PPARα and PPARδ. Rosiglitazone-induced interaction between PPARγ ligand binding domain (LBD) and coactivator SRC-1 was blocked by LFE or FSB, whereas reduced NCoR-1 binding to PPARγ by rosiglitazone was reversed in the presence of LFE or FSB. In vivo administration of LFE into either ob/ob mice or KKAy mice reduced body weights, and levels of PPARγ and C/EBPα in fat tissues. Furthermore, insulin resistance was ameliorated by LFE treatment, with reduced adipose tissue inflammation and hepatic steatosis. Thus, LFE and FSB were found to act as PPARγ antagonists that improve insulin sensitivity and metabolic profiles. We propose that LFE and its active component FSB offer a new therapeutic strategy for metabolic disorders including obesity and insulin resistance.
authors.affiliation: Department of Pharmacology, Gachon University School of Medicine, Incheon, Republic of Korea.
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Kwak
authors.affiliation: Department of Pharmacology, Gachon University School of Medicine, Incheon, Republic of Korea.
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Choi
authors.affiliation: Department of Pharmacology, Gachon University School of Medicine, Incheon, Republic of Korea.
authors.forename: Jinsun
authors.initials: J
authors.lastname: Jang
authors.affiliation: Department of Pharmacology, Gachon University School of Medicine, Incheon, Republic of Korea.
authors.forename: Soo Kyoung
authors.initials: SK
authors.lastname: Park
authors.affiliation: Natural Substance Research Team, Pharmaceutical R&D center, Kolmar Korea Co. Ltd., Sejong, Republic of Korea.
authors.forename: Byoung Heon
authors.initials: BH
authors.lastname: Cho
authors.affiliation: Natural Substance Research Team, Pharmaceutical R&D center, Kolmar Korea Co. Ltd., Sejong, Republic of Korea.
authors.forename: Seul Ki
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Sunyi
authors.initials: S
authors.lastname: Lee
authors.affiliation: Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Nam Sook
authors.initials: NS
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, Gachon University School of Medicine, Incheon, Republic of Korea.|Gachon Medical Research Institute, Gil Medical Center, Incheon, Republic of Korea.
authors.forename: Hyae Gyeong
authors.initials: HG
authors.lastname: Cheon
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D029623:Primulaceae / Q000737:chemistry*; D011485:Protein Binding; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D047495:PPAR gamma; D012503:Saponins; C570547:foenumoside B