Honokiol exerts dual effects on browning and apoptosis of adipocytes.

Abstract

Induction of brown adipocyte-like phenotype (browning) in white adipocytes and promotion of apoptosis by dietary and pharmacological compounds is considered a novel strategy against obesity. Here, we show that honokiol exerts dual modulatory effects on adipocytes via induction of browning in 3T3-L1 white adipocytes and apoptosis as well as activation of HIB1B brown adipocytes combined with inhibition of apoptosis. Honokiol-induced browning and apoptosis were investigated by determining expression levels of brown adipocyte-specific genes and proteins by RT-PCR and immunoblot analysis, respectively. Apoptotic data were validated by immunofluorescence and ROS levels were measured by FACS analysis. Honokiol treatment induced browning by elevating expression levels of brown adipocyte-specific genes such as Cidea, Cox8, Fgf21, Pgc-1α, and Ucp1. Honokiol promoted apoptosis of 3T3-L1 white adipocytes and inhibited apoptosis of HIB1B brown adipocytes via opposite regulation of the pro-apoptotic protein BAX and anti-apoptotic protein Bcl-2. Honokiol also significantly increased protein expression levels of ACOX1, CPT1, p-HSL, and p-PLIN and reduced ROS levels, suggesting its possible role in fat oxidation and lipid catabolism. Honokiol-induced browning could be mediated by activation of ERK, as inhibition of ERK by FR180204 abolished expression of PGC-1α and UCP1. Our findings suggest that honokiol exhibits a modulatory role in adipocytes via induction of browning and apoptosis in white adipocytes, promotion of catabolic lipid metabolism, as well as activation and inhibition of apoptosis in HIB1B brown adipocytes, thereby exhibiting therapeutic potential against obesity.