Downregulation of β1,4-galactosyltransferase 5 improves insulin resistance by promoting adipocyte commitment and reducing inflammation.
Downregulation of β1,4-galactosyltransferase 5 improves insulin resistance by promoting adipocyte commitment and reducing inflammation.
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β 1,4-半乳糖基转移酶 5 的下调可通过促进脂肪细胞定向和减少炎症来改善胰岛素抵抗
DOI：
10.1038/s41419-017-0239-5
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发表时间：
2018-02-07
影响因子：
9
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Li SF;Zhu CS;Wang YM;Xie XX;Xiao LL;Zhang ZC;Tang QQ;Li X
蛋白质糖基化是一种重要的翻译后修饰。异常糖基化与蛋白质分布和生物学功能的改变有关，因此与许多疾病有关。结果表明，β1，4-半乳糖基转移酶5（B4 GalT 5）的表达与糖尿病和肥胖呈正相关。在体内，皮下脂肪组织中的B4 GalT 5敲低减轻了胰岛素抵抗和脂肪组织炎症，并增加了高脂饮食（HFD）喂养的小鼠和ob/ob小鼠的脂肪形成。前脂肪细胞中B4 GalT 5的下调在骨形态发生蛋白（BMP）2/4治疗的情况下诱导向脂肪细胞谱系的定型，这通常是成脂定型所必需的。RNAi沉默实验显示B4 GalT 5敲低通过1A和2型BMP受体激活Smad和p38 MPAK信号通路。值得注意的是，B4 GalT 5敲低降低了BMPRIA糖基化，但增加了BMPRIA稳定性和细胞定位，从而导致BMPRIA的重新分布和BMP信号通路的激活。同时，下调B4 GalT 5表达可减少HFD小鼠和ob/ob小鼠皮下脂肪组织中巨噬细胞浸润和M1巨噬细胞标志物的表达。在骨髓源性巨噬细胞（BMDM）和RAW264.7细胞中，B4 GalT 5敲低也通过减少NFκB和JNK信号传导抑制M1标志物。这些结果证明B4 GalT 5下调通过促进脂肪形成定型和减少M1巨噬细胞浸润改善胰岛素抵抗。
Protein glycosylation is an important post-translational modification. Aberrant glycosylation has been implicated in many diseases because of associated changes in protein distribution and biological function. We showed that the expression of β1, 4-galactosyltransferase 5 (B4GalT5) was positively correlated with diabetes and obesity. In vivo, B4GalT5 knockdown in subcutaneous adipose tissue alleviated insulin resistance and adipose tissue inflammation, and increased adipogenesis in high-fat diet (HFD)-fed mice and ob/ob mice. Downregulation of B4GalT5 in preadipocyte cells induced commitment to the adipocyte lineage in the absence of bone morphogenetic protein (BMP) 2/4 treatment, which is typically essential for adipogenic commitment. RNAi silencing experiments showed B4GalT5 knockdown activated Smad and p38 MPAK signaling pathways through both type 1A and 2 BMP receptors. Remarkably, B4GalT5 knockdown decreased BMPRIA glycosylation but increased BMPRIA stability and cellular location, thus leading to redistribution of BMPRIA and activation of the BMP signaling pathway. Meanwhile, downregulation of B4GalT5 decreased the infiltration of macrophages and the markers of M1 macrophages in subcutaneous adipose tissue of HFD mice and ob/ob mice. In bone marrow-derived macrophages (BMDMs) and RAW264.7cells, B4GalT5 knockdown also repressed the markers of M1 by reducing NFκB and JNK signaling. These results demonstrated B4GalT5 downregulation improved insulin resistance by promoting adipogenic commitment and decreasing M1 macrophage infiltration.
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影响因子：
64.5
作者：
Lau, Ken S.;Partridge, Emily A.;Dennis, James W.
通讯作者：
Dennis, James W.
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.7
作者：
Chen, Chia-Hua;Wang, Shui-Hua;Huang, Min-Chuan
通讯作者：
Huang, Min-Chuan
DOI：
10.1359/jbmr.090806
发表时间：
2010-02
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Kamiya N;Kobayashi T;Mochida Y;Yu PB;Yamauchi M;Kronenberg HM;Mishina Y
通讯作者：
Mishina Y
肿瘤坏死因子-α的脂肪表达--在与肥胖相关的胰岛素抵抗中的直接作用
影响因子：
56.9
作者：
HOTAMISLIGIL, GS;SHARGILL, NS;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM