Leu Sy-Ying, Chen Yi-Chen, Tsai Yung-Chieh, Hung Yao-Wen, Hsu Chih-Hsiung, Lee Yen-Mei, Cheng Pao-Yun
Graduate Institute of Life Sciences, National Defense Medical Center , 114 Taipei, Taiwan.
Department of Physiology and Biophysics, Graduate Institute of Physiology, National Defense Medical Center , 114 Taipei, Taiwan.
J Agric Food Chem. 2017 Dec 20;65(50):10907-10914. doi: 10.1021/acs.jafc.7b03831. Epub 2017 Dec 11.
This study aimed to determine the antiobesity effects of raspberry ketone (RK), one of the major aromatic compounds contained in raspberry, and its underlying mechanisms. During adipogenesis of 3T3-L1 cells, RK (300 μM) significantly reduced lipid accumulation and downregulated the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferation-activated receptor γ (PPARγ), fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS). RK also reduced the expression of light chain 3B (LC3B), autophagy-related protein 12 (Atg12), sirtuin 1 (SIRT1), and phosphorylated-tuberous sclerosis complex 2 (TSC2), whereas it increased the level of p62 and phosphorylated-mammalian target of rapamycin (mTOR). Daily administration of RK decreased the body weight (ovariectomy [Ovx] + RK, 352.6 ± 5 vs Ovx, 386 ± 5.8 g; P < 0.05), fat mass (Ovx + RK, 3.2 ± 0.05 vs Ovx, 5.0 ± 0.4 g; P < 0.05), and fat cell size (Ovx + RK, 6.4 ± 0.6 vs Ovx, 11.1 ± 0.7 × 10 μm; P < 0.05) in Ovx-induced obesity in rats. The expression of PPARγ, C/EBPα, FAS, and FABP4 was significantly reduced in the Ovx + RK group compared with that in the Ovx group. Similar patterns were observed in autophagy-related proteins and endoplasmic reticulum stress proteins. These results suggest that RK inhibited lipid accumulation by regulating autophagy in 3T3-L1 cells and Ovx-induced obese rats.
本研究旨在确定树莓酮（RK）（树莓中含有的主要芳香化合物之一）的抗肥胖作用及其潜在机制。在3T3-L1细胞的脂肪生成过程中，RK（300μM）显著减少脂质积累，并下调CCAAT/增强子结合蛋白α（C/EBPα）、过氧化物酶体增殖物激活受体γ（PPARγ）、脂肪酸结合蛋白4（FABP4）和脂肪酸合酶（FAS）的表达。RK还降低了轻链3B（LC3B）、自噬相关蛋白12（Atg12）、沉默调节蛋白1（SIRT1）和磷酸化结节性硬化复合物2（TSC2）的表达，而增加了p62和磷酸化雷帕霉素靶蛋白（mTOR）的水平。每日给予RK可降低去卵巢（Ovx）诱导的肥胖大鼠的体重（Ovx + RK组为352.6±5 g，Ovx组为386±5.8 g；P < 0.05）、脂肪量（Ovx + RK组为3.2±0.05 g，Ovx组为5.0±0.4 g；P < 0.05）和脂肪细胞大小（Ovx + RK组为6.4±0.6×10μm，Ovx组为11.1±0.7×10μm；P < 0.05）。与Ovx组相比，Ovx + RK组中PPARγ、C/EBPα、FAS和FABP4的表达显著降低。在自噬相关蛋白和内质网应激蛋白中也观察到类似模式。这些结果表明，RK通过调节3T3-L1细胞和Ovx诱导的肥胖大鼠中的自噬来抑制脂质积累。
