Boiling-Resistant Single-Chain Sweet Protein Monellin as a Safe and Effective Sugar Alternative for Metabolic and...

The global rise in obesity and metabolic disorders has intensified the demand for safe and effective sugar alternatives. Monellin, a naturally sweet protein derived from Dioscoreophyllum cumminsii, serves as an excellent sugar alternative, but its broader application has been constrained by poor thermal stability and limited evaluation of long-term metabolic effects. In this study, we evaluated the metabolic effects of MNEI-Mut6, a boiling-resistant single-chain monellin variant, in male C57BL/6 mice fed standard chow supplemented with either 4% sucrose or an equivalent sweetness concentration of MNEI-Mut6 for 16 weeks. Compared with sucrose, MNEI-Mut6 did not promote weight gain, preserved insulin sensitivity, and maintained glucose homeostasis. In addition, MNEI-Mut6 reduced hepatic lipid accumulation and adipocyte hypertrophy without inducing hepatotoxic or nephrotoxic effects. Collectively, these findings demonstrate that MNEI-Mut6, a thermally stable and metabolically neutral sweetener, is a promising and safer alternative to sucrose and artificial sweeteners suitable for application in food processing and product formulation.