Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity
Adipose-specific deletion of Kif5b exacerbates obesity and insulin resistance in a mouse model of diet-induced obesity
复制标题
Kif5b 的脂肪特异性缺失会加剧饮食诱导肥胖小鼠模型的肥胖和胰岛素抵抗
DOI：
10.1096/fj.201601103r
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发表时间：
2017-06-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Tie-Mei
中科院分区：
文献类型：
--
作者：
Cui, Ju;Pang, Jing;Zhang, Tie-Mei
最近的研究表明，KIF 5 B（重链中的常规生物碱）介导3 T3-L1脂肪细胞中葡萄糖转运蛋白4的转位和脂联素的分泌，提示KIF 5 B参与代谢的稳态。然而，KIF 5 B在脂肪组织中的体内生理功能仍有待确定。在本研究中，使用Cre-LoxP策略产生脂肪特异性Kif 5 b敲除（F-K5 bKO）小鼠。F-K5 bKO小鼠的体重与饲喂标准饲料的对照组相似。然而，F-K5 bKO小鼠具有高脂血症和显著的葡萄糖耐受不良和胰岛素抵抗。Kif 5 b的缺失加重了高脂饮食（HFD）对体重增加、脂肪肝、葡萄糖耐量和全身胰岛素敏感性的有害影响。这些变化伴随着受损的胰岛素信号，减少分泌脂联素，血清瘦素和促炎性脂肪因子水平的增加。喂食HFD的F-K5 bKO小鼠表现出较低的能量消耗和产热功能障碍，这是由于线粒体生物合成减少和关键产热基因表达下调导致棕色脂肪变白的结果。总之，脂肪组织中Kif 5 b的选择性缺失加剧了HFD诱导的肥胖及其相关的代谢紊乱，部分原因是能量消耗减少，脂肪因子分泌失调和胰岛素信号传导。崔，J.，Pang，J.，林，Y.- J.，龚，H.，王志- H、李，Y. X.，李杰，王志，江，P.，Dai，D.- P.，李杰，蔡杰P.，黄杰D、张，T.- M.脂肪特异性Kif 5 b缺失在饮食诱导的肥胖小鼠模型中加重肥胖和胰岛素抵抗
Recent studies haveshownthatKIF5B (conventionalkinesin heavy chain) mediates glucose transporter type 4 translocation and adiponectin secretion in 3T3-L1 adipocytes, suggesting an involvement of KIF5B in the homeostasis of metabolism. However, the in vivo physiologic function ofKIF5B in adipose tissue remains to be determined. In this study, adipose-specific Kif5b knockout (F-K5bKO) mice were generated using the Cre-LoxP strategy. F-K5bKO mice had similar body weights to controls fed on a standard chow diet. However, F-K5bKO mice had hyperlipidemia and significant glucose intolerance and insulin resistance. Deletion of Kif5b aggravated the deleterious impact of a high-fat diet (HFD) on body weight gain, hepatosteatosis, glucose tolerance, and systematic insulin sensitivity. These changes were accompanied by impaired insulin signaling, decreased secretion of adiponectin, and increased serum levels of leptin and proinflammatory adipokines. F-K5bKO mice fed on an HFD exhibited lower energy expenditure and thermogenic dysfunction as a result of whitening of brown adipose due to decreased mitochondria biogenesis and down regulation of key thermogenicgene expression. In conclusion, selective deletion of Kif5b in adipose tissue exacerbates HFD-induced obesity and its associated metabolic disorders, partly through a decrease in energy expenditure, dysregulation of adipokine secretion, and insulin signaling.-Cui, J., Pang, J., Lin, Y.-J., Gong, H., Wang, Z.-H., Li, Y.-X., Li, J., Wang, Z., Jiang, P., Dai, D.-P., Li, J., Cai, J.-P., Huang, J.-D., Zhang, T.-M. Adipose-specific deletionof Kif5b exacerbates obesity and insulin resistance in a mousemodel of diet-induced obesity.