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Endothelial IGF‐1 receptor mediates crosstalk with the gut wall to regulate microbiota in obesity
Author(s) -
Haywood Natalie J,
Luk Cheukyau,
Bridge Katherine I,
Drozd Michael,
Makava Natallia,
Skromna Anna,
Maccannell Amanda,
Ozber Claire H,
Warmke Nele,
Wilkinson Chloe G,
Watt Nicole T,
KochPaszkowski Joanna,
Teh Irvin,
Boyle Jordan H,
Smart Sean,
Schneider Jurgen E,
Yuldasheva Nadira Y,
Roberts Lee D,
Beech David J,
Sukumar Piruthivi,
Wheatcroft Stephen B,
Cubbon Richard M,
Kearney Mark T
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202050767
Subject(s) - crosstalk , gut flora , microbiology and biotechnology , receptor , obesity , biology , immunology , endocrinology , genetics , physics , optics
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.