Orobol, an Enzyme-Converted Product of Genistein, Suppresses Obesity by Targeting Casein Kinase 1 epsilon

Abstract

Obesity is one of the most important risk factors in the various diseases including type 2 diabetes, cardiovascular diseases, and multiple forms of cancers. Due to side-effects of anti-obesity drugs, natural materials have been studied to be used as alternatives for obesity treatment. There have been many evidences that isoflavones derived from soybean play a beneficial role in obesity. In the present study, the anti-obesity effect of orobol which is one of soy isoflavones has been investigated in adipogenic cocktail (MDI)-induced 3T3-L1 adipocytes and high-fat diet (HFD)-induced male C57BL/6J obese mice model. During MDI-induced adipogenesis in 3T3-L1 pre-adipocytes, orobol 20 M suppressed lipid accumulation and decreased protein expression levels of peroxisome proliferator-activated receptor-γ (PPARγ), CCAT/ enhancer-binding protein-α (C/EBPα) and fatty acid synthase (FAS). Orobol blocked adipogenesis from early stage to terminal differentiation by inhibiting Casein Kinase 1 epsilon (CK1ε) and its downstream signaling pathways, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in 3T3-L1 preadipocytes. Also orobol treatment resulted in reduced lipid accumulation in HFD-fed mice model. In summary, I firstly identified orobol significantly suppressed adipogenesis and this inhibitory effect exerted through CK1ε/4E-BP1 in 3T3-L1 preadipocytes. These findings suggest orobol can be a novel therapeutic agent to treat obesity.