Gut Hormone Secretion by Dietary Maltooligosaccharide Chemosensation in Small Intestine Enteroendocrine Cells
Authors: El Hindawy Marwa Mohamed , Kim Choon Young , Hamaker Bruce R. 
Published: November 2023

The mechanism by which distal small intestine (ileum) exposure to unabsorbed macronutrients inhibits upper gut function (i.e. ileal brake) and hypothalamic appetite control are not fully understood. The gut peptides, glucagon‐like peptide‐1 (GLP‐1) and peptide YY (PYY), are secreted from the enteroendocrine L cells in the ileum and proximal colon and contribute to this mechanism. GLP‐1 exerts an anti‐hyperglycemic effect by slowing gastric emptying, reduces hepatic glucose productivity, and promotes satiety. Similarly, PYY plays a critical role in regulating energy homoeostasis and reducing food intake by acting on the neuropeptide Y (NPY) receptor in the central appetite circuit. A recent study in our laboratory showed that suppression of hypothalamic orexigenic neuropeptide expression in rats fed slowly digestible starch was concurrent with lower food intake compared to rats fed rapid digestible starch. This finding suggests that complex carbohydrates arriving the ileum can induce such physiological effect. It is not clear, however, whether it is α‐amylase starch degradation products, the maltooligosaccharides, or glucose itself, or even fermentation products (short chain fatty acids, SCFAs), in the ileum that cause this effect. Our hypothesis was that intestinal L cells are triggered by maltooligosaccharides and further exhibit different responses of gut hormone secretion with different carbohydrate structures and compared to SCFAs. To study the hypothesis we used the mouse enteroendocrine L cell line STC‐1, as well as the human model for L cells, NCI‐H716. After fasting the cells for 2 h, 25 mM of different maltooligosaccharides in PBS were used to treat cells for 2 h in a humidified incubator at 37 ºC and 5% CO2. GLP‐1 secretion was measured in the PBS supernatant using ELISA and normalized to total cellular protein content. Our results showed that maltooligosaccharides exhibit a unique effect on L cell sensitivity and gut hormone productivity. First, GLP‐1 secretion levels were significantly higher in the cells treated with maltooligosaccharides compared to glucose or propionate. Second, increasing size (degree of polymerization) of the maltooligosaccharide, from maltose to maltopentaose, incrementally increased GLP‐1 secretion. Maltotriose and maltopentaose showed up to 2‐fold increase in GLP‐1 levels (1.16 and 1.23 pM/μg protein respectively) compared to glucose (0.57 pM/μg protein). In addition, we confirmed the absence of any digestion ability of the cell lines to breakdown maltooligosaccharides into glucose, thus showing that the effect was due to the structure/size of the treatment molecules and not to accumulating glucose content. These results shed new light on the intricate role of dietary carbohydrates on gut physiological response, related to satiety and food intake. It is conceivably that bioactive carbohydrates could one day be designed to confer physiological outcomes related to type 2 diabetes treatment and obesity reduction.