Phlorotannins isolated from the edible brown alga Ecklonia stolonifera exert anti-adipogenic activity on 3T3-L1 adipocytes by downregulating C/EBPα and PPARγ

Abstract

The dramatic increase in obesity-related diseases emphasizes the need to elucidate the cellular and molecular mechanisms underlying fat metabolism. Inhibition of adipocyte differentiation has been suggested to be an important strategy for preventing or treating obesity. In our previous study, we characterized an Ecklonia stolonifera extract and non-polar fractions thereof, including dichloromethane and ethyl acetate fractions. We showed that these fractions inhibited adipocyte differentiation and lipid formation/accumulation in 3T3-L1 preadipocytes, as assessed by Oil Red O staining. As part of our ongoing search for anti-obesity agents derived from E. stolonifera, in this work, we characterized five known phlorotannins, including phloroglucinol, eckol, dieckol, dioxinodehydroeckol, and phlorofucofuroeckol A, all of which were isolated from the active ethyl acetate fraction of E. stolonifera. We determined the chemical structures of these phlorotannins through comparisons of published nuclear magnetic resonance (NMR) spectral data. Furthermore, we screened these phlorotannins for their abilities to inhibit adipogenesis over a range of concentrations (12.5-100 μM). Of these five phlorotannins, phloroglucinol, eckol, and phlorofucofuroeckol A significantly concentration-dependently inhibited lipid accumulation in 3T3-L1 cells without affecting cell viability. In addition, the five isolated phlorotannins also significantly reduced the expression levels of several adipocyte marker genes, including proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), although they did so to different extents. These results suggest that the molecular weight of a phlorotannin is an important factor affecting its ability to inhibit adipocyte differentiation and modulate the expression levels of adipocyte marker genes.

Keywords: 3T3-L1 cells; Adipocyte differentiation; C/EBPα; Ecklonia stolonifera; Obesity; PPARγ.