Impact of cassava-derived resistant starch type 3 on weight gain and hepatic lipid deposition and its association with SIRT1 and antioxidant responses in rats

Resistant starch (RS) is a dietary component with potential benefits for obesity and metabolic disorders. This study aimed to investigate the anti-adipogenic effects and associated molecular responses of cassava-derived RS type 3 (C-RS3). Thai native cassava starch (C-NS) was modified into C-RS3, and healthy male Wistar rats were fed diets containing C-NS (44.5 g%) or C-RS3 (38.1 g%) for 28 days. Despite comparable food intake and calorie intake, C-RS3-fed rats exhibited significantly attenuated body weight gain (15.9 ± 2.8%) compared to C-NS-fed rats (34.4 ± 2.6%; p < 0.001). This potent anti-adipogenic effect was confirmed by reduced liver and visceral fat weights, significantly lower serum triglycerides, and decreased hepatic lipid deposition. While overall systemic glucose homeostasis (AUC, fasting glucose, HOMA-IR index, insulin, and glucagon) remained unchanged, C-RS3 significantly lowered the initial glucose peak at 15 min post-load during the Oral Glucose Tolerance Test. The core finding of the molecular analysis was the significant elevation of SIRT1 protein in the liver and serum ( p < 0.05), despite no change in hepatic Sirt1 and Sirt3 mRNA levels. Furthermore, correlation analysis revealed a coordinated metabolic and redox-related associations, particularly positive correlation between sirtuin transcripts and antioxidant enzyme transcripts ( CAT , GPx , SOD ). These findings suggest that C-RS3 attenuates weight gain, adiposity, dyslipidemia, and hepatic lipid accumulation, accompanied by increased SIRT1 protein and coordinated sirtuin–antioxidant-related responses. However, the precise mechanisms underlying these effects require further investigation. C-RS3 may therefore represent a promising functional ingredient for metabolic health management.