Glutamine and alanyl-glutamine promote crypt expansion and mTOR signaling in murine enteroids

American Journal of Physiology. Gastrointestinal and Liver Physiology
Sean R MooreNoah F Shroyer

Abstract

L-glutamine (Gln) is a key metabolic fuel for intestinal epithelial cell proliferation and survival and may be conditionally essential for gut homeostasis during catabolic states. We show that L-alanyl-L-glutamine (Ala-Gln), a stable Gln dipeptide, protects mice against jejunal crypt depletion in the setting of dietary protein and fat deficiency. Separately, we show that murine crypt cultures (enteroids) derived from the jejunum require Gln or Ala-Gln for maximal expansion. Once expanded, enteroids deprived of Gln display a gradual atrophy of cryptlike domains, with decreased epithelial proliferation, but stable proportions of Paneth and goblet cell differentiation, at 24 h. Replenishment of enteroid medium with Gln selectively activates mammalian target of rapamycin (mTOR) signaling pathways, rescues proliferation, and promotes crypt regeneration. Gln deprivation beyond 48 h leads to destabilization of enteroids but persistence of EGFP-Lgr5-positive intestinal stem cells with the capacity to regenerate enteroids upon Gln rescue. Collectively, these findings indicate that Gln deprivation induces a reversible quiescence of intestinal stem cells and provides new insights into nutritional regulation of intestinal epithelial homeos...Continue Reading

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Citations

Mar 5, 2016·Archives of Disease in Childhood·Indi TrehanMark J Manary
May 17, 2017·JPEN. Journal of Parenteral and Enteral Nutrition·Yun ChenYa-Hui Tsai
May 11, 2017·Journal of Pediatric Gastroenterology and Nutrition·Suzanna AttiaRobert H J Bandsma
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Jul 11, 2020·Journal of Pediatric Gastroenterology and Nutrition·Sean R MooreAldo A M Lima
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Aug 3, 2017·Revista do Colégio Brasileiro de Cirurgiões·Isadora Moscardini Fabiani, Sérgio Luiz Rocha
Apr 29, 2020·Nutrients·Ricard FarréGianluca Matteoli
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Aug 23, 2020·Journal of Pediatric Gastroenterology and Nutrition·Sean R MooreAldo A M Lima
Mar 1, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Sanchita RauthMoorthy P Ponnusamy

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