Siraitia grosvenorii residue water extract granules regulate fat deposition via intestinal microbiota and its metabolites

Abstract Given the high global prevalence of obesity, the development of safe and effective natural ingredients for obesity intervention is urgently needed. Although Siraitia grosvenorii is a medicinal and edible plant, existing studies have focused on its refined components (e.g., mogrosides and polysaccharides), while the lipid-lowering capacity of its processing by-product ( S. grosvenorii residue) remains largely unclear. Here, we prepared water-extract granules from this residue (SGREG) via water extraction, concentration, and granulation, and evaluated their effects on lipid metabolism in high-fat diet (HFD)-induced obese and normal-diet mice. SGREG significantly inhibited body weight gain and fat deposition, ameliorated HFD-induced dyslipidemia (reduced serum TG, TC, and LDL-C) and hepatic dysfunction (lowered ALT and AST), and reduced food intake without causing compensatory hyperphagia. 16S rRNA sequencing revealed that SGREG selectively enriched beneficial bacteria ( Ligilactobacillus and Dubosiella ) and suppressed pro-inflammatory Desulfovibrionaceae , while increasing fecal short-chain fatty acids (acetate, propionate, butyrate). SGREG also upregulated colonic GLP-1 and PYY expression and restored ghrelin secretion. In normal-diet mice, SGREG slowed weight gain and optimized glucose and lipid profiles by modulating lipid synthesis ( FAS , ACC, and SREBP-1c ), lipolytic genes ( AMPKα and PPARα ) and LXRα-dependent transport genes ( CD36 and ApoA1 ). Collectively, SGREG alleviates HFD-induced obesity through coordinated regulation of gut microbiota, SCFAs, and gastrointestinal hormones, supporting the high-value utilization of S. grosvenorii residue as a natural intervention for obesity-related metabolic disorders.