Glutamine supplementation improves intestinal cell proliferation and stem cell differentiation in weanling mice

Abstract

BackgroundIntestinal stem cells can be differentiated into absorptive enterocytes and secretory cells, including Paneth cells, goblet cells, and enteroendocrine cells. Glutamine is a primary metabolic fuel of small intestinal enterocytes and is essential for the viability and growth of intestinal cells.ObjectiveWhether glutamine supplementation affects the differentiation of intestinal stem cells is unknown.DesignThree-week-old ICR (Institute of Cancer Research) male mice were divided randomly into two groups: 1) mice receiving a basal diet and normal drinking water and 2) mice receiving a basal diet and drinking water supplemented with glutamine. After 2 weeks, the mice were sacrificed to collect the ileum for analysis.ResultsThe study found that glutamine supplementation in weanling mice decreases the crypt depth in the ileum, leading to higher ratio of villus to crypt in the ileum, but promotes cell proliferation of intestinal cells and mRNA expression of Lgr5 (leucine-rich repeat-containing g-protein coupled receptor5) in the ileum. Glutamine has no effect on the number of Paneth cells and goblet cells, and the expression of markers for absorptive enterocytes, Paneth cells, goblet cells, and enteroendocrine cells.ConclusionThese findings reveal the beneficial effects of dietary glutamine supplementation to improve intestinal morphology in weanling mammals.

Review: The roles and functions of glutamine on intestinal health and performance of weaning pigs

“…For example, glutamine at a dosage of 2% did not promote mRNA expression in other Paneth cell-associated factors such as α-defensins (cryptdin-1, -4 and -5), lysozyme C and angiogenin 4 in the ileum of mouse models (Liu et al, 2017). Glutamine at a dosage of 10 mg/ml fed to weaning mice did not affect the number of absorptive enterocytes, Paneth cells, goblet cells, enteroendocrine cells or the gene expression of these cell markers (Chen et al, 2018a). However, the in vitro administration of 10 mmol glutamine increased chromogranin A and mucin 2 expression.…”

“…Intestinal epithelium developmental changes after weaning The gut includes crypts and villi, which are formed by four principal cell types: absorptive enterocytes, mucus-producing goblet cells, hormone-secreting enteroendocrine cells and lysozyme-containing Paneth cells (Chen et al, 2018a). The porcine intestinal epithelium structure is shown in Figure 1.…”

“…Glutamine has long been recognized as having an important role in cell survival and proliferation (Ehrensvard et al, 1949). Glutamine promotes intestinal cell proliferation in rats (Swaid et al, 2013), piglets (Wang et al, 2008) and various cell lines (Chen et al, 2018b). A recent study with weaning mice by Chen et al (2018a) found that 10 mg/ml glutamine promotes Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49), a stem cell marker, expression in intestinal cells.…”

“…Glutamine promotes intestinal cell proliferation in rats (Swaid et al, 2013), piglets (Wang et al, 2008) and various cell lines (Chen et al, 2018b). A recent study with weaning mice by Chen et al (2018a) found that 10 mg/ml glutamine promotes Lgr5 (leucine-rich-repeat-containing G-protein-coupled receptor 5, also known as Gpr49), a stem cell marker, expression in intestinal cells. Another study found that Lgr5 stem cell growth is closely associated with epidermal growth factor (EGF), Wnt3 and the Notchligand.…”

“…Further work is necessary to determine if and how glutamine changes these signal pathways to promote Lgr5 stem cell development. Some studies indicate that supplemental glutamine had no effect on lysozyme and angiogenin expressions that are Paneth cell markers (Liu et al, 2017;Chen et al, 2018a). For example, glutamine at a dosage of 2% did not promote mRNA expression in other Paneth cell-associated factors such as α-defensins (cryptdin-1, -4 and -5), lysozyme C and angiogenin 4 in the ileum of mouse models (Liu et al, 2017).…”