Abstract

Backgrounds Largemouth bass (Micropterus salmoides) is an economically important aquaculture species, but its pronounced intolerance to high‐carbohydrate diets often leads to metabolic liver disorders and compromised growth, limiting the practical application of cost‐effective high‐carbohydrate feeds in aquaculture. Lipid nanoparticles (LNPs) have shown promise in regulating glucose metabolism in mammals, but their efficacy and size‐dependent effects in fish remain unelucidated. Objective LNPs were evaluated as novel potential additives to enhance the glucose utilization in M. salmoides under high‐glucose (HG) feeding conditions, addressing the issues of glucose intolerance and thereby reducing breeding costs. Methods We constructed LNPs to serve as a feed additive for modulating the glucose metabolism in M. salmoides. We prepared LNPs with five different particle sizes (60, 125, 150, 175, and 200 nm) by varying the formulation ratio of the preparation. To obtain further results, the regulatory effect of LNPs on glucose metabolism in M. salmoides was verified through gavage administration. The expression levels of genes associated with glucose metabolism in M. salmoides were observed following acute (one administration) treatment with HG feeding to investigate the relevance between LNPs and glucose metabolism induced by HG in M. salmoides. Results HG exposure activated the hepatic PI3K/AKT pathway, upregulated the expression of gluconeogenesis‐related genes (foxo1 and g6pase), and disrupted the expression of glycogenesis‐related genes (gsk3 and gys1), leading to impaired glucose metabolism in M. salmoides—a key pathogenesis of high‐carbohydrate‐induced metabolic disorders.