A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells.
A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells.
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DOI：
10.1371/journal.pone.0054500
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shibata H
中科院分区：
文献类型：
--
作者：
Masubuchi Y;Nakagawa Y;Ma J;Sasaki T;Kitamura T;Yamamoto Y;Kurose H;Kojima I;Shibata H
甜味受体不仅在味蕾中表达，而且在肠道内分泌细胞、胰岛β细胞等非味觉器官中也有表达，可能在能量代谢中发挥更广泛的生理作用。在这里，我们研究了甜味受体在3T3-L1细胞中的表达和功能。在未分化的前脂肪细胞中，T1R2和T1R3的表达都很弱，而T1R3的表达在诱导分化后明显上调(在第6天分别上调了83.0倍和3.8倍)。在整个分化过程中，Gs(GαS)和G14(Gα14)的Gustducin亚基均有表达，但不表达Gustducin。在分化的前48小时加入三氯蔗糖或糖精显著降低了过氧化体增殖物激活受体γ(PPARγ)和CCAAT/增强子结合蛋白α(C/EBPα)的表达，在第4天抑制了aP2的表达，在第6天抑制了甘油三酯的积累。这些抗脂肪作用可被短发夹状RNA介导的T1R3基因沉默所减弱。此外，GαS显性负性突变体的过表达，而不是Gα14的抑制剂YM-254890的过表达，抑制了甜味剂的作用，表明Gs可能与甜味感受器偶联。一致地，三氯蔗糖和糖精增加了分化中的3T3-L1细胞和异源表达T1R3的HEK293细胞中cAMP的浓度。此外，甜味剂的抗成脂作用可被霍乱毒素激活的Gs所模拟，但不能被Forsklin激活的腺苷环化酶所模拟，而小干扰核糖核酸介导的GαS的抑制作用则相反。3T3-L1细胞表达一种功能性的甜味感受器，它可能是一种T1R3异构体，它通过Gs依赖但cAMP不依赖的机制介导抗脂肪信号。
Sweet taste receptor is expressed not only in taste buds but also in nongustatory organs such as enteroendocrine cells and pancreatic beta-cells, and may play more extensive physiological roles in energy metabolism. Here we examined the expression and function of the sweet taste receptor in 3T3-L1 cells. In undifferentiated preadipocytes, both T1R2 and T1R3 were expressed very weakly, whereas the expression of T1R3 but not T1R2 was markedly up-regulated upon induction of differentiation (by 83.0 and 3.8-fold, respectively at Day 6). The α subunits of Gs (Gαs) and G14 (Gα14) but not gustducin were expressed throughout the differentiation process. The addition of sucralose or saccharin during the first 48 hours of differentiation considerably reduced the expression of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (C/EBPα at Day 2, the expression of aP2 at Day 4 and triglyceride accumulation at Day 6. These anti-adipogenic effects were attenuated by short hairpin RNA-mediated gene-silencing of T1R3. In addition, overexpression of the dominant-negative mutant of Gαs but not YM-254890, an inhibitor of Gα14, impeded the effects of sweeteners, suggesting a possible coupling of Gs with the putative sweet taste-sensing receptor. In agreement, sucralose and saccharin increased the cyclic AMP concentration in differentiating 3T3-L1 cells and also in HEK293 cells heterologously expressing T1R3. Furthermore, the anti-adipogenic effects of sweeteners were mimicked by Gs activation with cholera toxin but not by adenylate cyclase activation with forskolin, whereas small interfering RNA-mediated knockdown of Gαs had the opposite effects. 3T3-L1 cells express a functional sweet taste-sensing receptor presumably as a T1R3 homomer, which mediates the anti-adipogenic signal by a Gs-dependent but cAMP-independent mechanism.
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影响因子：
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作者：
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通讯作者：
Ullrich, Axel
影响因子：
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