The modulatory effect of pea resistant starch on hyperlipidemia in high fat diet‐induced obese mice is related to their supramolecular structural features

Abstract BACKGROUND Resistant starch (RS) has gained attention for its potential in managing metabolic disorders. This study aimed to compare the supramolecular structure and anti‐hyperlipidemia effects of RS isolated from native pea starch (NP‐RS) and autoclaved pea starch (AP‐RS) in high‐fat diet (HFD)‐induced obese mice. The structural characteristics of NP‐RS and AP‐RS were analyzed, and their impacts on obesity‐related conditions, gene expression, and gut microbiota were evaluated. RESULTS The crystalline polymorph of AP‐RS shifted from a C‐type to a B‐type, with significantly higher long‐ and short‐range crystallinity and double helix levels compared to NP‐RS, as determined by X‐ray diffraction and solid‐state carbon‐13 nuclear magnetic resonance ( 13 C‐NMR) analyses. Small‐angle X‐ray scattering analysis demonstrated a higher α value for AP‐RS, suggested enhanced structural compactness. In vivo experiments revealed that both NP‐RS and AP‐RS alleviated obesity‐related conditions, including body weight control, oxidative stress inhibition, inflammatory response alleviation, and liver function regulation, with AP‐RS exhibiting more pronounced effects. These effects were associated with the down‐regulation of gene expression levels of liver type glycogen synthase‐2 (GYS2), enzyme glycogenin‐1 (GYG1), sterol regulatory element binding protein‐1 (SREBP‐1), fatty acid synthase (FAS) and the up‐regulation of insulin induced gene‐1 (Insig‐1), Insig‐2, and acetyl‐CoA oxidase 1 (Acox1). Additionally, 16S rDNA sequencing analysis indicated that both NP‐RS and AP‐RS mitigated HFD‐induced gut dysbiosis by increasing the abundance of beneficial bacteria, such as Allobaculum and Bifidobacterium . CONCLUSION The resistant characteristics of AP‐RS, marked by increased crystallinity and a higher content of double helices, exhibit greater stability. This stability likely leads to differences in accessibility and fermentability between NP‐RS and AP‐RS substrates in vivo across various intestinal segments, resulting in different physiological responses in obese mice. These findings highlight the potential for designing novel RS‐based supplements with tailored metabolic effects to promote health benefits. © 2025 Society of Chemical Industry.