Fucosterol inhibits adipogenesis through modulation of FoxO pathway in 3T3-L1 cells

Abstract

Fucosterol isolated from Ecklonia stolonifera, is a sterol metabolite reported to have multiple biological functions such as the prevention of diabetic complications, anti-cholinesterase, anti-oxidative and anti-inflammatory activities. However, molecular mechanisms involved in anti-obesity activity of fucosterol have not been fully elucidated. The purpose of this study is to investigate the effects of fucosterol on adipogenesis of 3T3-L1 preadipocytes and its underlying mechanisms. Fucosterol significantly reduced intracellular lipid accumulation of 3T3-L1 adipocytes at concentrations of 25 and 50 μM. It also decreased expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1 (SREBP-1). Subsequently, fucosterol down-regulated insulin-triggered phosphatidylinositide 3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK) pathways and enhanced Sirtuin 1 (SirT1) expression, resulting in increased activity of Forkhead box protein O1 (FoxO1). In conclusion, fucosterol inhibits adipogenesis of 3T3-L1 adipocytes through modulation of FoxO signaling pathway. Therefore, fucosterol could possibly be one of novel agents for the treatment of obesity.