Regulation of hepatic glucose metabolism by lipid nanoparticles in largemouth bass (Micropterus salmoides)

The aims of this study were to explore the impact of lipid nanoparticles (LNPs) on glucose metabolism in Micropterus salmoides and gain further insights into the underlying mechanisms through which LNPs enhance glucose utilization. First, to examine the effects of LNPs on the glucose metabolism of Micropterus salmoides following a short-term administration of glucose solution, five different treatments were conducted: normal saline solution (Saline group), glucose solution (Glu group), glucose solution + LNPs solution (Glu+LNPs group), glucose solution + siGCGRa (Glu+siGCGR group), and glucose solution + LNPs solution + siGCGRa (Glu+LNPs+siGCGR group). The findings demonstrated a significant inhibition of gluconeogenesis in both the siGCGR group and LNPs group within 12 h following oral gavage of glucose solution. Then, to explore the effects of LNPs on the glucose metabolism of Micropterus salmoides fed different carbohydrate diets over a 4-week experimental period, the fish were separated into two groups based on diet: the 10 % carbohydrate diet (C10) and the 18 % carbohydrate diet (C18). Each dietary group was further subdivided into four treatment groups: Control, LNPs, siGCGR, and LNPs+siGCGR. The Control group received normal saline, while the other groups were treated with LNPs, siGCGRa, or the combination of LNPs and siGCGRa, respectively. It was observed that C18 feeding led to impaired glucose tolerance; however, no such alteration was observed in the LNPs and siGCGR groups. Meanwhile, although C18 feeding suppressed gluconeogenesis and enhanced glycolytic pathway to some extent, administration of LNPs via gavage and siGCGRa injection exerted a more pronounced inhibitory effect on gluconeogenesis while promoting the glycolytic pathway. Consequently, insulin sensitivity was restored to normal levels in largemouth bass. No significant differences in glucose utilization and insulin sensitivity were observed between the groups with siGCGR+LNPs and the siGCGR, suggesting that LNPs may enhance glucose metabolism through gcgr inhibition. • Lipid nanoparticles (LNPs) inhibited the gluconeogenesis process in largemouth bass. • LNPs can promote the glycolytic pathway of largemouth bass. • LNPs reduced blood glucose levels in largemouth bass.