The anti-obesity effects of a tuna peptide on 3T3-L1 adipocytes are mediated by the inhibition of the expression of lipogenic and adipogenic genes and by the activation of the Wnt/β-catenin signaling pathway.
The anti-obesity effects of a tuna peptide on 3T3-L1 adipocytes are mediated by the inhibition of the expression of lipogenic and adipogenic genes and by the activation of the Wnt/β-catenin signaling pathway.
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DOI：
10.3892/ijmm.2015.2231
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发表时间：
2015-08
影响因子：
5.4
通讯作者：
Nam TJ
中科院分区：
文献类型：
--
作者：
Kim YM;Kim IH;Choi JW;Lee MK;Nam TJ
3 T3-L1细胞向脂肪细胞的分化涉及肥胖相关基因的有组织系统的激活，其中编码CCAAT/增强子结合蛋白（C/EBP）和Wnt-10 b蛋白的基因可能起着不可或缺的作用。在我们以前的研究中，我们发现在金枪鱼中发现的一种特异性肽（序列D-I-V-D-K-I-E-I;称为TP-D）抑制3 T3-L1细胞分化。在本研究中，我们观察到C/EBP和Wnt-10 b的表达与肥胖相关。3 T3-L1细胞分化的初始步骤涉及C/EBP-α表达的上调，这反过来激活了各种子因子。糖原合成酶激酶-3 β（GSK-3β）的上游效应子抑制3 T3-L1脂肪细胞中Wnt-10 b的表达。在我们先前的研究中，我们通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）和四极杆飞行时间质谱（Q-TOF MS/MS）对金枪鱼肽进行测序，并证实其在3 T3-L1脂肪细胞中的抗肥胖作用。在本研究中，我们证明TP-D抑制C/EBP和促进Wnt-10 b mRNA的表达，从而激活Wnt通路。使用葡萄糖和甘油三酯（TG）测定来测量脂质蓄积的抑制。我们的结果证实TP-D以剂量依赖的方式改变C/EBP相关基因的表达水平，并激活Wnt信号通路。此外，我们证实，总脂联素和高分子量（HMW）脂联素水平与TP-D治疗降低。这些数据表明，TP-D通过抑制C/EBP基因和随后激活Wnt/β-连环蛋白信号通路来抑制脂肪细胞分化。
The differentiation of 3T3-L1 cells into adipocytes involves the activation of an organized system of obesity-related genes, of which those encoding CCAAT/enhancer-binding proteins (C/EBPs) and the Wnt-10b protein may play integral roles. In a previous study of ours, we found that a specific peptide found in tuna (sequence D-I-V-D-K-I-E-I; termed TP-D) inhibited 3T3-L1 cell differentiation. In the present study, we observed that the expression of expression of C/EBPs and Wnt-10b was associated with obesity. The initial step of 3T3-L1 cell differentiation involved the upregulation of C/EBP-α expression, which in turn activated various subfactors. An upstream effector of glycogen synthase kinase-3β (GSK-3β) inhibited Wnt-10b expression in 3T3-L1 adipocytes. In a previous study of ours, we sequenced the tuna peptide via sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and quadrupole time-of-flight mass spectrometry (Q-TOF MS/MS) and confirmed the anti-obesity effects thereof in 3T3-L1 adipocytes. In the present study, we demonstrate that TP-D inhibits C/EBP and promotes Wnt-10b mRNA expression, thus activating the Wnt pathway. The inhibition of lipid accumulation was measured using a glucose and triglyceride (TG) assay. Our results confirmed that TP-D altered the expression levels of C/EBP-related genes in a dose-dependent manner and activated the Wnt signaling pathway. In addition, we confirmed that total adiponectin and high-molecular weight (HMW) adiponectin levels were reduced by treatment with TP-D. These data indicate that TP-D inhibits adipocyte differentiation through the inhibition of C/EBP genes and the subsequent activation of the Wnt/β-catenin signaling pathway.