Endothelial IGF-1 receptor mediates crosstalk with the gut wall to regulate microbiota in obesity.
Endothelial IGF-1 receptor mediates crosstalk with the gut wall to regulate microbiota in obesity.
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DOI：
10.15252/embr.202050767
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发表时间：
2021-05-05
期刊：
影响因子：
7.7
通讯作者：
Kearney MT
中科院分区：
文献类型：
--
作者：
Haywood NJ;Luk C;Bridge KI;Drozd M;Makava N;Skromna A;Maccannell A;Ozber CH;Warmke N;Wilkinson CG;Watt NT;Koch-Paszkowski J;Teh I;Boyle JH;Smart S;Schneider JE;Yuldasheva NY;Roberts LD;Beech DJ;Sukumar P;Wheatcroft SB;Cubbon RM;Kearney MT
Changes in composition of the intestinal microbiota are linked to the development of obesity and can lead to endothelial cell (EC) dysfunction. It is unknown whether EC can directly influence the microbiota. Insulin‐like growth factor‐1 (IGF‐1) and its receptor (IGF‐1R) are critical for coupling nutritional status and cellular growth; IGF‐1R is expressed in multiple cell types including EC. The role of ECIGF‐1R in the response to nutritional obesity is unexplored. To examine this, we use gene‐modified mice with EC‐specific overexpression of human IGF‐1R (hIGFREO) and their wild‐type littermates. After high‐fat feeding, hIGFREO weigh less, have reduced adiposity and have improved glucose tolerance. hIGFREO show an altered gene expression and altered microbial diversity in the gut, including a relative increase in the beneficial genus Akkermansia. The depletion of gut microbiota with broad‐spectrum antibiotics induces a loss of the favourable metabolic differences seen in hIGFREO mice. We show that IGF‐1R facilitates crosstalk between the EC and the gut wall; this crosstalk protects against diet‐induced obesity, as a result of an altered gut microbiota. It remained unclear if gut endothelial cells can directly influence the microbiota. Here, endothelial specific over‐expression of IGF‐1R is shown to promote advantageous remodelling of the gut microbiota upon high fat diet, which protects against the development of obesity.
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影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
5.2
作者：
Cani PD;de Vos WM
通讯作者：
de Vos WM
影响因子：
7.7
作者：
Imrie H;Viswambharan H;Sukumar P;Abbas A;Cubbon RM;Yuldasheva N;Gage M;Smith J;Galloway S;Skromna A;Rashid ST;Futers TS;Xuan S;Gatenby VK;Grant PJ;Channon KM;Beech DJ;Wheatcroft SB;Kearney MT
通讯作者：
Kearney MT
影响因子：
82.9
作者：
Depommier, Clara;Everard, Amandine;Cani, Patrice D.
通讯作者：
Cani, Patrice D.