Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.
PLoS One. 2013 Jul 25;8(7):e69925. doi: 10.1371/journal.pone.0069925. Print 2013.
This study examined the anti-obesity effect and mechanism of action of blueberry peel extracts (BPE) in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. The levels of lipid accumulation were measured, along with the changes in the expression of genes and proteins associated with adipocyte differentiation in 3T3-L1 cells. Evidenced by Oil-red O staining and triglyceride assay, BPE dose-dependently inhibited lipid accumulation at concentrations of 0, 50, and 200 µg/ml. BPE decreased the expression of the key adipocyte differentiation regulator C/EBPβ, as well as the C/EBPα and PPARγ genes, during the differentiation of preadipocytes into adipocytes. Moreover, BPE down-regulated adipocyte-specific genes such as aP2 and FAS compared with control adipocytes. The specific mechanism mediating the effects of BP revealed that insulin-stimulated phosphorylation of Akt was strongly decreased, and its downstream substrate, phospho-GSK3β, was downregulated by BPE treatment in 3T3-L1 cells. Together, these data indicated that BP exerted anti-adipogenic activity by inhibiting the expression of PPARγ and C/EBPβ and the Akt signaling pathway in 3T3-L1 adipocytes. Next, we investigated whether BP extracts attenuated HFD-induced obesity in rats. Oral administration of BPE reduced HFD-induced body weight gain significantly without affecting food intake. The epididymal or perirenal adipose tissue weights were lower in rats on an HFD plus BPE compared with the tissue weights of HFD-induced obese rats. Total cholesterol and triglyceride levels in the rats fed BPE were modestly reduced, and the HDL-cholesterol level was significantly increased in HFD plus BP-fed rats compared with those of HFD-fed rats. Taken together, these results demonstrated an inhibitory effect of BP on adipogenesis through the down-regulation of C/EBPβ, C/EBPα, and PPARγ and the reduction of the phospho-Akt adipogenic factor in 3T3-L1 cells. Moreover, BPE reduced body weight gain and inhibited fat accumulation in an HFD-induced animal model of obesity.
本研究旨在探讨蓝莓皮提取物（BPE）在 3T3-L1 细胞和高脂饮食（HFD）诱导肥胖大鼠中的抗肥胖作用及其作用机制。通过油红 O 染色和甘油三酯测定法测量脂质积累水平，并检测与 3T3-L1 细胞中脂肪细胞分化相关的基因和蛋白质的变化。结果表明，BPE 在 0、50 和 200µg/ml 浓度下呈剂量依赖性地抑制脂质积累。BPE 降低了关键脂肪细胞分化调节因子 C/EBPβ以及 C/EBPα 和 PPARγ 基因在前脂肪细胞向脂肪细胞分化过程中的表达。此外，与对照脂肪细胞相比，BPE 下调了脂肪细胞特异性基因，如 aP2 和 FAS。BP 介导作用的具体机制表明，胰岛素刺激的 Akt 磷酸化强烈减少，其下游底物磷酸化 GSK3β 也被 BPE 处理下调。综上所述，这些数据表明 BP 通过抑制 3T3-L1 脂肪细胞中 PPARγ 和 C/EBPβ 的表达以及 Akt 信号通路来发挥抗脂肪生成活性。接下来，我们研究了 BP 提取物是否能减轻大鼠的 HFD 诱导肥胖。BPE 的口服给药可显著降低 HFD 诱导的体重增加，而不影响食物摄入。与 HFD 诱导肥胖大鼠相比，HFD 加 BPE 组大鼠的附睾或肾周脂肪组织重量较低。BPE 喂养的大鼠总胆固醇和甘油三酯水平略有降低，HFD 加 BP 喂养的大鼠高密度脂蛋白胆固醇水平显著升高。综上所述，这些结果表明 BP 通过下调 C/EBPβ、C/EBPα 和 PPARγ 以及降低 3T3-L1 细胞中的磷酸化 Akt 脂肪生成因子来抑制脂肪生成。此外，BPE 可降低体重增加并抑制肥胖动物模型中脂肪的积累。
