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Publication
Endothelial IGF-1 receptor mediates crosstalk with the gut wall to regulate
microbiota in obesity.
Authors 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
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal EMBO reports
Year 2021
Date Published 5/1/2021
Volume : Pages 22 : e50767
PubMed Reference 33934497
Abstract 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.




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