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Requirement for the intestinal epithelial insulin‐like growth factor‐1 receptor in the intestinal responses to glucagon‐like peptide‐2 and dietary fat
Author(s) -
Markovic Melanie A.,
Srikrishnaraj Arjuna,
Tsang Derek,
Brubaker Patricia L.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000169r
Subject(s) - enterocyte , medicine , endocrinology , glucagon like peptide 2 , chylomicron , cd36 , triglyceride , insulin like growth factor , biology , receptor , growth factor , chemistry , small intestine , lipoprotein , biochemistry , very low density lipoprotein , cholesterol , peptide
The intestinal hormone, glucagon‐like peptide‐2 (GLP‐2), enhances the enterocyte chylomicron production. However, GLP‐2 is known to require the intestinal‐epithelial insulin‐like growth factor‐1 receptor (IE‐IGF‐1R) for its other actions to increase intestinal growth and barrier function. The role of the IE‐IGF‐1R in enterocyte lipid handling was thus tested in the GLP‐2 signaling pathway, as well as in response to a Western diet (WD). IE‐IGF‐1R knockout (KO) and control mice were treated for 11 days with h(GLY 2 )GLP‐2 or fed a WD for 18 weeks followed by a duodenal fat tolerance test with C 14 ‐labeled triolein. Human Caco‐2BBE cells were treated with an IGF‐1R antagonist or signaling inhibitors to determine triglyceride‐associated protein expression. The IE‐IGF‐1R was required for GLP‐2‐induced increases in CD36 and FATP‐4 in chow‐fed mice, and for expression in vitro; FATP‐4 also required PI3K/Akt. Although WD‐fed IE‐IGF‐1R KO mice demonstrated normal CD36 expression, the protein was incorrectly localized 2h post‐duodenal fat administration. IE‐IGF‐1R KO also prevented the WD‐induced increase in MTP and decrease in APOC3, increased jejunal mucosal C 14 ‐fat accumulation, and elevated plasma triglyceride and C 14 ‐fat levels. Collectively, these studies elucidate new roles for the IE‐IGF‐1R in enterocyte lipid handling, under basal conditions and in response to GLP‐2 and WD‐feeding.