A branched α-glucan from Galli Gigeriae Endothelium Corneum alleviates high-fat diet-induced obesity in a gut microbiota-dependent manner

A highly branched α-glucan, designated GE0A, was isolated from Galli Gigeriae Endothelium Corneum and investigated for its structural characteristics, gastrointestinal fate, and metabolic effects in diet-induced obesity. GE0A had a weight-average molecular weight of 85.0kDa and consisted exclusively of glucose. Methylation and NMR analyses revealed a branched α-glucan composed predominantly of α-(1→4)-linked glucopyranosyl sequences with O-6 branch points. During simulated digestion, GE0A remained stable in salivary and gastric phases but was partially depolymerized into lower-molecular-weight oligosaccharides during the intestinal phase. Following oral administration, Cy5-labeled GE0A-derived material remained largely confined to the gastrointestinal tract, reached the cecum and colon, and showed partial association with F4/80-positive intestinal macrophages. During in vitro fecal fermentation, GE0A-derived carbohydrates were efficiently utilized by gut microbiota, accompanied by microbial growth and increased acetate and propionate production. In high-fat diet-fed mice, oral GE0A reduced body-weight gain without altering food intake, attenuated adipose accumulation and hepatic steatosis, improved glucose and lipid homeostasis, and enhanced cold tolerance and brown-adipose UCP1 and TOMM20 expression. GE0A also alleviated systemic and tissue inflammation, oxidative stress, and PI-positive damaged cells. Antibiotic-mediated microbiota depletion largely attenuated these metabolic and thermogenic benefits, whereas transplantation of microbiota from GE0A-treated donors was associated with partial recovery of several metabolic responses, supporting a microbiota-dependent mechanism. Collectively, these findings indicate that GE0A behaves as a fermentable dietary-fiber-like α-glucan that undergoes partial intestinal depolymerization and is subsequently utilized by gut microbiota to generate short-chain fatty acids associated with improved metabolic homeostasis.