Dieckol, a major phlorotannin in Ecklonia cava, suppresses lipid accumulation in the adipocytes of high-fat diet-fed zebrafish and mice: Inhibition of early adipogenesis via cell-cycle arrest and AMPKα activation.

Abstract

Dieckol is a major polyphenol of Ecklonia cava. This study demonstrates a mechanistic role for dieckol in the suppression of lipid accumulation using three models. Mice were split into four experimental groups (n = 10 per group): normal diet, high-fat diet (HFD), and dieckol-supplemented diets. Dieckol-supplemented mice groups showed a significant decrease of body weight gain (38%) as well as fats of organs including epididymal (45%) compared with a HFD-fed group. LDL cholesterol level was reduced by 55% in dieckol-supplemented group. Adipogenic factors and lipid synthetic enzymes were analyzed via real-time PCR or immunoblotting. Dieckol regulated mRNA expressions of early adipogenic genes in 3T3-L1 cells. These results were reflected in downregulation of late adipogenic factors, resulting in a decrease in triacylglycerol content. These data were also verified in zebrafish and mouse models. Dieckol activated AMP-activated protein kinase α (AMPKα) signaling to inhibit lipid synthesis in 3T3-L1 and mouse model. Dieckol was also shown to inhibit mitotic clonal expansion via cell-cycle arrest. Our data demonstrate that dieckol inhibits lipid accumulation via activation of AMPKα signaling and cell-cycle arrest.