Extensive metabolic disorders are present in APCmin tumorigenesis mice
Extensive metabolic disorders are present in APCmin tumorigenesis mice
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APC(min) 肿瘤发生小鼠存在广泛的代谢紊乱
DOI：
10.1016/j.mce.2016.03.004
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发表时间：
2016-05-15
影响因子：
4.1
通讯作者：
Duan, Qiong
中科院分区：
文献类型：
--
作者：
Liu, Zhenzhen;Xiao, Yi;Duan, Qiong
Wnt信号在间充质干细胞（MSC）分化中起重要作用。Wnt信号的激活抑制脂肪形成，但促进MSC中的骨形成。腺瘤性结肠息肉病（APC）是β-连环蛋白和Wnt信号传导活性的负调节剂。APC基因突变导致Wnt信号通路激活，是APC（min）小鼠肿瘤发生的重要机制，但对其代谢异常的研究较少。本研究报告了广泛的代谢紊乱表型在APC（分钟）小鼠。老年APC（min）小鼠体重下降，脂肪形成障碍，但高脂血症严重，表现为家族性腺瘤性息肉病（FAP），这是一种由APC基因突变引起的人类遗传性疾病。结果发现，APC（min）小鼠白色脂肪组织（WAT）中脂质代谢和游离脂肪酸（FA）利用基因的表达明显低于对照组。这种基因表达模式的改变可能导致WAT时循环脂质转运和储存功能障碍。此外，APC（min）小鼠不能在寒冷条件下维持核心体温。PET-CT测定显示，APC（min）小鼠的BAT从血液中摄取（18）FDG的能力显著受损。形态学研究表明，APC（min）小鼠的棕色脂肪细胞充满脂滴，但线粒体较少。这些结果与APC（min）小鼠中BAT功能受损的发现相匹配。总的来说，我们的研究探索了一种新的机制，解释了APC（min）小鼠的异常代谢，并为研究FAP患者的代谢紊乱提供了见解。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Wnt signaling plays essential role in mesenchymal stem cell (MSC) differentiation. Activation of Wnt signaling suppresses adipogenesis, but promotes osteogenesis in MSC. Adenomatous polyposis coli (APC) is a negative regulator of beta-catenin and Wnt signaling activity. The mutation of APC gene leads to the activation of Wnt signaling and is responsible for tumorigenesis in APC(min) mouse; however, very few studies focused on its metabolic abnormalities. The present study reports a widespread metabolic disorder phenotype in APC(min) mice. The old APC(min) mice have decreased body weight and impaired adipogenesis, but severe hyperlipidemia, which mimic the phenotypes of Familial Adenomatous Polyposis (FAP), an inherited disease also caused by APC gene mutation in human. We found that the expression of lipid metabolism and free fat acids (FA) use genes in the white adipose tissue (WAT) of the APC(min) mice is much lower than those of control. The changed gene expression pattern may lead to the disability of circulatory lipid transportation and storage at WAT. Moreover, the APC(min) mice could not maintain the core body temperature in cold condition. PET-CT determination revealed that the BAT of APC(min) mice has significantly impaired ability to take up (18)FDG from the blood. Morphological studies identified that the brown adipocytes of APC(min) mice were filled with lipid droplets but fewer mitochondria. These results matched with the findings of impaired BAT function in APC(min) mice. Collectively, our study explores a new mechanism that explains abnormal metabolism in APC(min) mice and provides insights into studying the metabolic disorders of FAP patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.