title: Regulation of adipocytokine secretion and adipocyte hypertrophy by polymethoxyflavonoids, nobiletin and tangeretin.
abstract: OBJECTIVE
  The polymethoxyflavonoids nobiletin and tangeretin possess several important biological properties such as neuroprotective, antimetastatic, anticancer, and anti-inflammatory properties. The present study was undertaken to examine whether nobiletin and tangeretin could modulate adipocytokine secretion and to evaluate the effects of these flavonoids on the hypertrophy of mature adipocytes.
  
  
  METHODS
  All experiments were performed on the murine preadipocyte cell line 3T3-L1. We studied the formation of intracellular lipid droplets in adipocytes and the apoptosis-inducing activity to evaluate the effects of polymethoxyflavonoids on adipocyte differentiation and hypertrophy, respectively. The secretion of adipocytokines was measured using ELISA.
  
  
  RESULTS
  We demonstrated that the combined treatment of differentiation reagents with nobiletin or tangeretin differentiated 3T3-L1 preadipocytes into adipocytes possessing less intracellular triglyceride as compared to vehicle-treated differentiated 3T3-L1 adipocytes. Both flavonoids increased the secretion of an insulin-sensitizing factor, adiponectin, but concomitantly decreased the secretion of an insulin-resistance factor, MCP-1, in 3T3-L1 adipocytes. Furthermore, nobiletin was found to decrease the secretion of resistin, which serves as an insulin-resistance factor. In mature 3T3-L1 adipocytes, nobiletin induced apoptosis; tangeretin, in contrast, did not induce apoptosis, but suppressed further triglyceride accumulation.
  
  
  CONCLUSIONS
  Our results suggest that nobiletin and tangeretin are promising therapeutic candidates for the prevention and treatment of insulin resistance by modulating the adipocytokine secretion balance. We also demonstrated the different effects of nobiletin and tangeretin on mature adipocytes.
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suwarashi, Midori, Sagamihara, Kanagawa 252-5195, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyata
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Arata
authors.initials: A
authors.lastname: Shimada
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yamanouchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kosano
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D054392:Adipokines / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D049108:Cell Enlargement / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D003470:Culture Media; D004797:Enzyme-Linked Immunosorbent Assay; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007333:Insulin Resistance; D051379:Mice; D015394:Molecular Structure; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D054392:Adipokines; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003470:Culture Media; D047309:Flavones; D014280:Triglycerides; C008661:nobiletin; C059006:tangeretin