Optimized Cirsium setidens Nakai Fermented by Lentinula edodes Attenuates Lipid Accumulation by Regulating Fatty Acid Oxidation-mediated Lipolysis in 3T3-L1 Cells and High Calorie Diet-induced Obese Zebrafish

Cirsium setidens Nakai is an edible herb. Previously we found that fermented Cirsium setidens Nakai (FCSN) has a large amount of major bioactive compound compared to Cirsium setidens Nakai. In this study, we aimed to examine the anti-obesity effect of FCSN using 3T3-L1 cells in vitro and high calorie diet-induced obese (HDIO) zebrafish model in vivo. Our results demonstrated that FCSN significantly inhibited intracellular lipid accumulation in 3T3-L1 cells. FCSN was shown to reduce the expressions of crucial adipocyte differentiation markers, including PPARγ and aP2. FCSN also decreased the production of ROS due to the up-regulated expressions of SOD1, SOD2, GPx, and catalase. Furthermore, we observed that FCSN also altered the levels of energy metabolism and β-oxidation-associated genes such as AMPK, ACC, and CPT-1. In addition, ATGL, a key lipolysis enzyme, was stimulated while the differentiation of 3T3-L1 was suppressed by FCSN. Strikingly, we found that FCSN dramatically increased both the energy metabolism and β-oxidation associated genes and subsequently prevented the increase of body fat accumulation in high calorie diet-induced obese zebrafish. Taken together, this is the first study that demonstrates that FCSN has the beneficial activity to suppress adipogenesis in 3T3-L1 cells and ameliorate an obese-associated health condition in vivo.