High-amylose maize starch as a functional carbohydrate: Long-term regulation of glucose homeostasis following early-life intervention.

Carbohydrate intake in early life drives long-term host metabolic homeostasis. Maternal obesity is recognized as a risk factor for metabolic disorders in offspring. High-amylose maize starch (HAMS) is a functional carbohydrate with metabolic regulatory capabilities. However, its mechanisms and potential effects in improving glucose metabolism disorders in offspring with maternal obesity during early life remain unexplored. Here, we characterized the structural properties of HAMS and assessed its structural stability during gastrointestinal digestion. Subsequently, using a high-fat diet-induced maternal obesity model, we evaluated the long-term effects of early-life HAMS supplementation (3-8 weeks) on glucose metabolism in offspring and explored the potential mechanisms, focusing on hormone secretion, pancreatic islet function, and hepatic metabolomics. HAMS supplementation significantly improved glucose metabolism disorders in offspring with maternal obesity. Mechanistically, in vitro digestion experiments demonstrated that HAMS partially escaped gastrointestinal digestion and delivered increased amounts of fermentable carbohydrates to the colon. HAMS digestion products activated intestinal L-cells, restoring maternal obesity-induced reductions in serum glucagon-like peptide-1 (GLP-1) levels. HAMS also significantly increased GLP-1R, Ngn3, and Pdx1 gene expression, promoting pancreatic β-cell neogenesis and enhancing insulin secretion. Furthermore, hepatic metabolomics revealed that HAMS intake activated insulin signaling and energy metabolism-related pathways, including the AMPK, PI3K-Akt, and FoxO signaling pathways, and modulated amino acid metabolic networks in offspring with maternal obesity. This study provides new insights for investigating the regulatory role of HAMS in glucose metabolism and indicates that HAMS may serve as an effective dietary strategy in early life to improve glucose homeostasis in offspring with maternal obesity.