Non-digestible stachyose reverses overnutrition-induced insulin resistance via stimulating the secretion of glucagon-like peptide-1.

Stachyose is a commonly utilized natural additive due to its profound metabolism-improving properties, but the molecular mechanisms underlying its metabolism-regulatory activities remain largely unknown. This study reveals that oral supplementation with stachyose reverses overnutrition-induced insulin resistance, hyperglycemia and dyslipidemia, which is accompanied by ameliorated adipose tissue remodeling and alleviated liver steatosis. RNA-seq and immunoblot analysis indicate that stachyose restores AKT phosphorylation in peripheral metabolic organs. The mechanistic study indicates that stachyose stimulates glucagon-like peptide-1 (GLP-1) secretion from enteroendocrine L-cells via the cyclic adenosine monophosphate (cAMP)/L-type calcium channel cascade, while co-administration of a GLP-1 receptor antagonist abolishes the metabolic benefits of stachyose in overweight mice. These findings reveal that a novel enteroendocrine mechanism underlies the metabolic benefits of stachyose, which strengthens the scientific foundation for developing stachyose as a food-based strategy for metabolic health management.