Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk 712-714, Republic of Korea.
Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk 712-714, Republic of Korea.
Pharmacol Rep. 2017 Dec;69(6):1357-1365. doi: 10.1016/j.pharep.2017.06.004. Epub 2017 Jun 19.
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.
通过饮食和药物化合物诱导白色脂肪细胞棕色表型（褐变）和促进细胞凋亡被认为是对抗肥胖的一种新策略。在这里，我们表明，厚朴酚通过诱导 3T3-L1 白色脂肪细胞褐变以及凋亡和激活 HIB1B 棕色脂肪细胞并抑制凋亡，对脂肪细胞具有双重调节作用。
通过 RT-PCR 和免疫印迹分析分别测定棕色脂肪细胞特异性基因和蛋白的表达水平来研究厚朴酚诱导的褐变和凋亡。通过免疫荧光验证凋亡数据，并通过 FACS 分析测量 ROS 水平。
厚朴酚处理通过提高棕色脂肪细胞特异性基因（如 Cidea、Cox8、Fgf21、Pgc-1α 和 Ucp1）的表达水平诱导褐变。厚朴酚促进 3T3-L1 白色脂肪细胞凋亡，并通过对促凋亡蛋白 BAX 和抗凋亡蛋白 Bcl-2 的相反调节来抑制 HIB1B 棕色脂肪细胞的凋亡。厚朴酚还显著增加 ACOX1、CPT1、p-HSL 和 p-PLIN 的蛋白表达水平并降低 ROS 水平，表明其在脂肪氧化和脂质分解代谢中可能具有作用。厚朴酚诱导的褐变可能是通过 ERK 的激活介导的，因为通过 FR180204 抑制 ERK 可消除 PGC-1α 和 UCP1 的表达。
我们的研究结果表明，厚朴酚通过诱导白色脂肪细胞褐变和凋亡、促进分解代谢脂质代谢、激活和抑制 HIB1B 棕色脂肪细胞凋亡，对脂肪细胞具有调节作用，从而具有治疗肥胖的潜力。
