Starch Digestion Products Activate Enteroendocrine L-cells and Their Ileal Delivery Through the Diet Contributes to Weight Management in Mice (P08-005-19)

OBJECTIVES: Our laboratory has recently shown that slowly digestible starch (SDS) that locationally digests to the ileum activates the gut-brain axis and reduces food intake in obese animals. Glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY) are the main appetite-suppressing (anorexigenic) peptides of the intestinal enterendocrine L-cells that regulate postprandial insulin levels and satiety signals. We investigated the in vitro L-cell chemosensation of α-amylase starch digestion products, named maltooligosaccharides (MOS), and using SDS to deliver MOS in vivo. METHODS: Mouse (STC-1) and human (NCI-H716) cells were used to test chemosensation response and release of GLP-1, OXM and PYY after MOS treatment. Differential gene expression and comparable global protein profiling of STC-1 cell treated with MOS was tested using RNA sequencing and LC-MS/MS analysis. Alginate-entrapped SDS microspheres that digest distally into the ileum were used to examine the role of SDS in the intervention and prevention of obesity in C57BL/6 J obese and lean mice, respectively. Body weight, food intake and body composition were monitored periodically. RESULTS: MOS exhibited significantly higher stimulatory effect on GLP-1 and OXM secretion in mouse and human L-cells, respectively, compared to glucose. Multi-omics analysis showed that MOS induced exocytosis of GLP-1- and OXM-containing vesicles and did not induce positive regulation of the proglucagon gene suggesting that secretion, but not synthesis, of the proglucagon gene products was enhanced by MOS. In vivo Results showed that 20% SDS in low-fat diets significantly improved weight loss and food intake reduction in obese mice. Similarly, 15% SDS in high-fat diets showed significant reduction in body fat %, increase in lean body mass, and considerable reduction in weight gain rate and food intake in lean mice fed on high-fat diets. CONCLUSIONS: We propose several insights into L-cell sensation of dietary starch-degraded MOS delivered by the consumption of slowly digestible starch. MOS exhibit unique influences on L-cell sensitivity and gut hormone productivity. The intricate role of dietary carbohydrates on gut physiological response, related to satiety and food intake could be a new approach for design of foods for obesity prevention. FUNDING SOURCES: Whistler Center for Carbohydrate Research, Purdue University. Supporting Tables, Images and/or Graphs