Regulation of adipocytokine secretion and adipocyte hypertrophy by polymethoxyflavonoids, nobiletin and tangeretin

• Published in: Life sciences (1973) Vol. 88; no. 13-14; pp. 613 - 618
• Main Authors: Miyata, Yoshiki, Tanaka, Haruyuki, Shimada, Arata, Sato, Takashi, Ito, Akira, Yamanouchi, Toshikazu, Kosano, Hiroshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 28.03.2011
• Subjects: 3T3-L1 Cells; adipocytes; Adipocytes - drug effects; Adipocytes - secretion; Adipokines - secretion; Adiponectin; Animals; anti-inflammatory activity; Apoptosis; Apoptosis - drug effects; Blotting, Western; Cell Culture Techniques; Cell Differentiation - drug effects; Cell Enlargement - drug effects; Chemokine CCL2 - secretion; Culture Media; droplets; Enzyme-Linked Immunosorbent Assay; Flavones - chemistry; Flavones - pharmacology; flavonoids; hypertrophy; In Situ Nick-End Labeling; Insulin Resistance; Mice; Molecular Structure; Monocyte chemoattractant protein; neuroprotective effect; Nobiletin; Polymethoxyflavonoid; Resistin; secretion; Tangeretin; Time Factors; triacylglycerols; Triglycerides - metabolism; Polymethoxyflavonoid; Nobiletin; Monocyte chemoattractant protein; Tangeretin; Adiponectin; Resistin; Apoptosis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2011.01.024

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. 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. 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. 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.