Dual Modulation of Lipid Metabolism by Adzuki Bean (Vigna angularis) Saponins Involving PPARα/γ Signaling and Gut Microbiota Remodeling in Obesogenic Diet-Induced Obese Mice

Obesity is a prevalent metabolic disorder characterized by excessive lipid accumulation. This study aimed to investigate the anti-obesity effects and underlying mechanisms of two triterpenoid saponin-rich extracts, designated disaccharide saponin-rich extract (DTS) and trisaccharide/tetrasaccharide saponin-rich extract (TTS), prepared from adzuki bean (Vigna angularis). In vitro, both DTS and TTS extracts significantly inhibited lipid accumulation in 3T3-L1 adipocytes without cytotoxicity, with TTS reducing lipid droplets to 21.45% of the model group at 200 μg/mL. In vivo, C57BL/6J mice were fed a high-fat–high-cholesterol diet (HFD) for 12 weeks and orally administrated with DTS or TTS (30, 60, or 120 mg/kg/day) via gavage; the results showed marked reductions in body weight gain (up to 20.37%), fat mass, liver coefficient, and serum levels of total cholesterol (TC), triglyceride (TG), Low-Density Lipoprotein Cholesterol (LDL-C), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST), while elevating high-density lipoprotein cholesterol (HDL-C) levels. Mechanistically, transcriptomics and Western blot analyses revealed that both extracts were associated with upregulation of the PPARα-ACOX1 axis, consistent with enhanced fatty acid β-oxidation, and downregulation of the PPARγ-FABP4 pathway, consistent with reduced adipogenesis, suggesting a dual shift toward lipid catabolism and away from lipid synthesis. Furthermore, 16S rRNA sequencing demonstrated that both saponin extracts reversed HFD-induced gut dysbiosis by restoring α-diversity and orchestrating distinct genus-level modulations, specifically suppressing obesity-associated pathobionts (Faecalibaculum and Ileibacterium) while concurrently enriching beneficial commensals (Bifidobacterium). Notably, TTS at 120 mg/kg reduced body weight gain to a greater extent than the positive control orlistat (p < 0.05, Tukey’s HSD), with comparable improvements in serum lipid profiles and liver function parameters. Collectively, these findings demonstrate that adzuki bean saponin extracts exert anti-obesity effects in HFD-fed mice and are associated with multi-target changes involving the “liver–adipose–gut axis,” supporting their further evaluation as candidate as functional food ingredients for metabolic health.