title: Cyclolepis genistoides D. Don (palo azul) promotes differentiation of adipocytes and regulates adipokine expression.
abstract: Cyclolepis genistoides D. Don is a herbaceous perennial belonging to the family Asteraceae, and its vernacular name is "palo azul" (palo). Palo has been reported to exhibit many physiological effects that contribute to the prevention of metabolic syndromes, although its mechanism is unclear. Among palo's various activities, we investigated the hypothesis that palo promotes adipocytes differentiation and regulates adipokine profiles in 3T3-L1 adipocytes by modulation of peroxisome proliferator-activated receptor (PPAR) γ, a major regulator of adipose differentiation. 3T3-L1 adipocytes were cultured and differentiated in Dulbecco modified Eagle medium with 50 to 200 μg/mL palo for 7 days or were cultured with palo without differentiation protocol for 14 days. Palo down-regulated the expression of 2 types of expressed/secreted adipokines, leptin and resistin, in a concentration-dependent manner. Under a nondifferentiated condition, palo promoted the accumulation of lipid droplets in cells. Real-time polymerase chain reaction and luciferase reporter assay showed that palo up-regulated expression and transcriptional activity of PPARγ. Furthermore, palo increased the expression of insulin-sensitizing adipokine, adiponectin, which is a directly target of PPARγ, both at the messenger RNA level and at the protein level. In summary, palo demonstrated the potential to improve insulin resistance by promoting adipocyte differentiation via PPARγ activation. Results suggest an increase in adiponectin secretion and a decrease in insulin-resistant factors such as leptin and resistin.
authors.affiliation: Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan. Electronic address: hiromi-s@chiba-u.jp.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sato
authors.forename: Momoko
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Asami
authors.initials: A
authors.lastname: Funaki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kimura
authors.forename: Hiroya
authors.initials: H
authors.lastname: Yoshida
authors.forename: Hideki
authors.initials: H
authors.lastname: Fukata
authors.forename: Hideo
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Ueno
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019659:Asteraceae; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D052243:Resistin / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D054392:Adipokines; D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D047495:PPAR gamma; D010936:Plant Extracts; D012333:RNA, Messenger; D052243:Resistin
keywords: 3T3-L1 cells; Adipocyte; Adipokine; DMEM; DMSO; Diabetes; Dulbecco modified Eagle medium; ELISA; FBS; HPLC; Insulin resistance; OA; PPAR response elements; PPARγ; PPREs; Palo; Palo azul; T2DM; UA; dimethyl sulfoxide; enzyme-linked immunosorbent assay; fetal bovine serum; high-performance liquid chromatography; oleanolic acid; palo azul; peroxisome proliferator–activated receptor γ; type 2 diabetic mellitus; ursolic acid