Novel black soy peptides with antiobesity effects: activation of leptin-like signaling and AMP-activated protein kinase

Objective: To investigate the mechanisms underlying the antiobesity effects of a novel isoflavone-free peptide mixture (BSP) derived from black soybean. Design: Long-term effects of BSP were evaluated in diet-induced obese (DIO) mice fed a high-fat (HF) diet without or with BSP (2, 5 or 10% of energy) for 13 weeks, or for 8 weeks in combination with exercise. Acute effects of BSP on food intake and body weight in rats and leptin-deficient ob/ob mice were evaluated. Cell culture models or tissue extracts were used to investigate the mechanisms underlying the antiobesity effect. Measurement: Total food intake, body weight gain, white adipose tissue (WAT) mass, plasma concentrations of leptin, adiponectin, cholesterol and triglyceride were measured. Janus kinase 2 (JAK2)-dependent signal transducers and activators of the transcription 3 (STAT3) phosphorylation and AMP-activated protein kinase (AMPK) activity were determined using Western-blot in cultured cells or tissue extracts. Results: DIO mice fed an HF diet with BSP (2, 5 or 10%) for 13 weeks gained less body weight (21.4, 19.8 or 17.1 g, respectively) than the mice fed an HF diet without BSP (22.6 g) concurrent with inhibition of total food intake in a dose-dependent manner. BSP also significantly decreased food intake in rats and leptin-deficient ob/ob mice. The highest dose of BSP (10%) significantly elevated the plasma adiponectin and decreased plasma triglyceride. BSP activated JAK2-dependent STAT3 in a cell model, and elevated the level of hypothalamic phospho-STAT3 in ob/ob mice. BSP also phosphorylated AMPK and acetylCoA carboxylase of C2C12 myocytes in a dose-dependent manner. The antiobesity effect was augmented by low-intensity wheel-based exercise. In exercised mice, BSP significantly decreased periepididymal WAT mass and body weight gain. Conclusion: These results provided evidences that BSP decreased appetite and HF diet-induced body weight gain particularly in combination with exercise, through leptin-like STAT3 phosphorylation and AMPK activation.