Oligonol, an oligomerized lychee fruit-derived polyphenol, activates the Ras/Raf-1/MEK1/2 cascade independent of the IL-6 signaling pathway in rat primary adipocytes.
Oligonol is a lychee fruit-derived low-molecular form of polyphenol. In this study, the effect of Oligonol on the mitogen activated-protein kinase (MAPK) signaling pathway in primary adipocytes was investigated to examine the mechanism underlying the enhanced levels of phosphorylated extracellular-signaling regulatory kinase1/2 (ERK1/2) that accompany an in vitro increase in lipolysis. Oligonol significantly elevated the levels of activated Ras and the phosphorylation of Raf-1 and MAPK/ERK kinase1/2 (MEK1/2) with no increase in pan-Raf-1 and -MEK1/2 proteins. The increase in phosphorylation of Raf-1 and MEK1/2 with Oligonol was inhibited completely by pretreatment with GW5074, a selective Raf-1 inhibitor, or PD98059, a selective MEK1/2 inhibitor. IL-6 also activated the MAPK signaling pathway in adipocytes through the association with its receptor. IL-6-induced phosphorylation of Raf-1 and MEK1/2 was significantly inhibited by pretreatment with the IL-6 receptor antibody. Under such a condition, however, the levels of phosphorylated Raf-1 and MEK1/2 with Oligonol still remained significantly higher, and there was a significant decrease in secretion of IL-6 from adipocytes, compared with untreated control cells. These results suggest that Oligonol activates the Ras/Raf-1/MEK1/2 signaling pathway, independent of the IL-6 signaling pathway, leading to activation of ERK1/2 proteins in primary adipocytes.
Ogasawara
Junetsu
J
Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, Mitaka, Tokyo 181-8611, Japan. junetsu@ks.kyorin-u.ac.jp
Kitadate
Kentaro
K
Nishioka
Hiroshi
H
Fujii
Hajime
H
Sakurai
Takuya
T
Kizaki
Takako
T
Izawa
Tetsuya
T
Ishida
Hitoshi
H
Tanno
Masataka
M
Ohno
Hideki
H
D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D032125:Litchi / Q000737:chemistry; D048369:MAP Kinase Kinase 1 / Q000096:biosynthesis; D048370:MAP Kinase Kinase 2 / Q000096:biosynthesis; D008297:Male; D009765:Obesity / Q000201:enzymology; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D019908:Proto-Oncogene Proteins c-raf / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018631:ras Proteins / Q000096:biosynthesis
D019440:Anti-Obesity Agents; D005419:Flavonoids; D015850:Interleukin-6; D010636:Phenols; D059808:Polyphenols; C514283:oligonol; D002392:Catechin; D019908:Proto-Oncogene Proteins c-raf; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D018631:ras Proteins