High fat diet exacerbates intestinal barrier dysfunction and changes gut microbiota in intestinal-specific ACF7 knockout mice
High fat diet exacerbates intestinal barrier dysfunction and changes gut microbiota in intestinal-specific ACF7 knockout mice
复制标题
高脂肪饮食加剧肠道屏障功能障碍并改变肠道特异性 ACF7 基因敲除小鼠的肠道微生物群
DOI：
10.1016/j.biopha.2018.11.100
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发表时间：
2019
影响因子：
7.5
通讯作者：
Yan Xuebing
中科院分区：
文献类型：
--
作者：
Shi Chenzhang;Li Hao;Qu Xiao;Huang Linsheng;Kong Cheng;Qin Huanlong;Sun Zhenliang;Yan Xuebing
微管-肌动蛋白交联因子-1(ACF7或MACF1)调节细胞骨架局部黏附动力学和在不同组织中的迁移。高脂饮食(HFD)可导致肠道微生物区系失调和代谢紊乱，增加肠道通透性和炎症反应。在这里，我们研究了肠道ACF7条件基因敲除(ACF7 CKO)和HFD对小鼠代谢表型、肠道微生物区系和肠道屏障功能的协同作用。ACF7CKO和对照组(ACF7fl/fl)小鼠(8周龄)分别饲喂饲料和高脂饲料，共16周。高脂饲料喂养的ACF7 CKO小鼠体重和脂肪垫重量的增加受到抑制，这可能是由于食物的摄取和吸收减少所致。与其他组相比，高脂饲料喂养的ACF7 CKO小鼠的代谢状态发生了显著变化。此外，与其他组相比，高脂饲料喂养的ACF7 CKO小鼠上皮细胞凋亡率、肠道通透性和炎症反应均增加。ACF7 CKO诱导的营养、肠道屏障功能和肠道微生物区系的改变与饮食治疗无关。综上所述，我们的研究首次证明HFD和ACF7 CKO对肠道内环境稳定具有协同破坏作用。ACF7在HFD诱导的肠道疾病中是一个重要的保护分子。
Microtubule-actin cross-linking factor-1 (ACF7, or MACF1) regulates cytoskeletal focal adhesion dynamics and migration in various tissues. High fat diet (HFD) induces gut microbiota dysbiosis and metabolic disorders, and increases intestinal permeability and inflammatory response. Here we investigated the synergistic effects of intestinal ACF7 conditional knockout (ACF7 cKO) and HFD on metabolism phenotypes, gut microbiota and intestinal barrier function in mice. ACF7 cKO and control (ACF7fl/fl) mice (8-week-old) were fed with either chow diet or HFD, for 16 weeks. The increase of body weight and fat pad weight were impaired in HFD-fed ACF7 cKO mice, which can be attributed to decreased food intake and absorption. The metabolic status of HFD-fed ACF7 cKO mice was dramatically changed when compared to the other groups. In addition, HFD-fed ACF7 cKO mice had increased epithelial cell apoptosis, intestinal permeability and inflammatory response when compared with the other groups. The ACF7 cKO-induced changes in alimentation, intestinal barrier function, and gut microbiota were independent of dietary treatment. Taken together, our studies for the first time proved HFD and ACF7 cKO have synergistic damaging effects on intestinal homeostasis. ACF7 is a crucial protective molecule in HFD-induced intestinal diseases.