Dietary red bean seedlings extract alleviates obesity via activation of PPARα - AMPKα signaling in white adipose tissue of high-fat diet-fed obese mice

With the global prevalence of obesity rising, there is an increasing need for the development of obesity treatments using natural substances with fewer side effects. The efficacy of germinated red bean extract and its bioactive compound, azukisaponin II (AZ), on anti-obesity has been reported very little to date. This study aims to investigate the anti-obesity effects of red bean seedling extract (RS) and AZ, on PPARα and AMPKα signaling pathways in white adipose tissue. RS supplementation effectively reduced fat mass and improved lipid metabolism in HFD-induced obese mice. RS decreased body weight gain, reduced adipocyte size, and lowered plasma triglyceride, free fatty acids, and total cholesterol. RS also enhanced mitochondrial function and fatty acid oxidation by activating AMPKα signaling and upregulating PPARα expression in white adipose tissue. In particular, the levels of lipolysis-related factors (ATGL, HSL, and PLIN5) and proteins in the mitochondrial electron transport chain (NDUFB8, SDHB, UQCRC2, MTCO1, ATP5A) were increased in the RS200 and RS300 groups. RS and AZ treatments inhibited adipogenesis and promoted lipid metabolism in 3T3-L1 adipocytes. Additionally, we confirmed that treating PPARα-knockdown 3T3-L1 cells with RS and AZ alleviates lipid accumulation by activating PPARα-AMPKα signaling. RS supplementation effectively reduces obesity in HFD-induced mice by enhancing lipid metabolism and mitochondrial function through PPARα-AMPKα signaling. Additionally, RS and AZ decrease lipid accumulation and promote mitochondrial biogenesis in 3T3-L1 cells, indicating their potential for treating obesity and metabolic disorders with a favorable safety profile.