Curcumin represses mouse 3T3-L1 cell adipogenic differentiation via inhibiting miR-17-5p and stimulating the Wnt signalling pathway effector Tcf7l2.
Curcumin represses mouse 3T3-L1 cell adipogenic differentiation via inhibiting miR-17-5p and stimulating the Wnt signalling pathway effector Tcf7l2.
复制标题
DOI：
10.1038/cddis.2016.455
复制
发表时间：
2017-01-19
影响因子：
9
通讯作者：
Jin T
中科院分区：
文献类型：
--
作者：
Tian L;Song Z;Shao W;Du WW;Zhao LR;Zeng K;Yang BB;Jin T
了解脂肪生成分化的机制可能会导致肥胖的新治疗靶点的发现。Wnt信号通路的激活导致脂肪生成分化受到抑制，而某些microrna可能调节前脂肪细胞的增殖和分化。我们在这里表明，在小鼠白色脂肪组织中，高脂肪饮食后miR-17-5p水平升高。miR-17-5p上调成脂分化，其过表达增加，而其抑制抑制3T3-L1分化。Tcf7l2基因编码一个关键的Wnt信号通路效应因子，其人类同源基因Tcf7l2是一个被高度重视的糖尿病风险基因。我们发现Tcf7l2是miR-17-5p的靶点，并证实了Tcf7l2对3T3-L1成脂分化的抑制作用。天然植物多酚化合物姜黄素具有减肥作用。我们观察到姜黄素在3T3-L1细胞中减弱miR-17-5p的表达并刺激Tcf7l2的表达。这些，以及小鼠附睾脂肪组织中miR-17-5p表达在高脂肪饮食消耗下的升高，使我们认为miR-17-5p是脂肪生成分化的中心开关之一。它通过抑制Wnt信号通路效应因子Tcf7l2激活脂肪形成，其自身的表达可能在健康和疾病中受到营养调节。
Understanding mechanisms underlying adipogenic differentiation may lead to the discovery of novel therapeutic targets for obesity. Wnt signalling pathway activation leads to repressed adipogenic differentiation while certain microRNAs may regulate pre-adipocyte proliferation and differentiation. We show here that in mouse white adipose tissue, miR-17-5p level is elevated after high fat diet consumption. miR-17-5p upregulates adipogenic differentiation, as its over-expression increased while its inhibition repressed 3T3-L1 differentiation. The Tcf7l2 gene encodes a key Wnt signalling pathway effector, and its human homologue TCF7L2 is a highly regarded diabetes risk gene. We found that Tcf7l2 is an miR-17-5p target and confirmed the repressive effect of Tcf7l2 on 3T3-L1 adipogenic differentiation. The natural plant polyphenol compound curcumin possesses the body weight lowering effect. We observed that curcumin attenuated miR-17-5p expression and stimulated Tcf7l2 expression in 3T3-L1 cells. These, along with the elevation of miR-17-5p expression in mouse epididymal fat tissue in response to high fat diet consumption, allowed us to suggest that miR-17-5p is among central switches of adipogenic differentiation. It activates adipogenesis via repressing the Wnt signalling pathway effector Tcf7l2, and its own expression is likely nutritionally regulated in health and disease.