Fagopyrum esculentum polysaccharides mitigate obesity by reshaping gut microbiota and enhancing lipid metabolism in high-fat diet-fed mice.

Recent findings suggest that the gut microbiota plays a vital role in linking dietary habits to the development of obesity. Natural polysaccharides have drawn significant interest as potential candidates for preventing and managing obesity by regulating the gut microbiota. Common buckwheat (Fagopyrum esculentum Moench) polysaccharides (FEP) possess antioxidant, anti-inflammatory, and microbiota-regulating properties, yet their anti-obesity potential remains largely unexplored. This study investigated the structural characteristics of FEP and its protective effects against obesity in mice fed a high-fat diet (HFD). FEP was characterized as a heat-stable polysaccharide with a molecular weight of 1.2 × 10 kDa, exhibiting a smooth, flake-like surface morphology and a high glucose content. In vivo, FEP supplementation significantly reduced body weight, OGTT levels, fatty liver, and lipid accumulation. It also enhanced antioxidant enzyme activities (SOD, catalase, GPx) and anti-inflammatory cytokines (IL-4, IL-10) while promoting fecal lipid and bile acid excretion. Additionally, FEP regulated glucose metabolism genes (G6Pase and GLUT2). Mechanistically, FEP enhanced lipolysis by upregulating AMPKα, ATGL, and HSL, promoted β-oxidation by increasing the expression of CPT-1 A, MCAD, SIRT1, PGC-1α, and PPARα, and regulated cholesterol metabolism through the activation of HMGCR, LXRα, and LXRβ. Meanwhile, it suppressed lipid synthesis pathways by downregulating ACC1α, C/EBPα, FAS, PPARγ, and SREBP1. Furthermore, FEP could inhibit obesity-related bacteria (Oscillibacter, Ruminococcus, and Dubosiella) and enhance short-chain fatty acids (SCFAs)-producing bacteria (Muribaculaceae, Enterorhabdus, and Bacteroides). The results suggest that FEP may help alleviate obesity by exerting antioxidant, anti-inflammatory, and gut microbiota-modulating effects, thereby highlighting its potential as a functional food ingredient for managing obesity.