Enteromorpha Polysaccharides Alleviate High‐Fat Diet‐Induced Glucolipid Metabolism Disorders via the K18‐Mediated IRS‐1/PI3K/AKT/GSK3β Pathway

Previous studies have shown that enteromorpha polysaccharide (EP) can improve glucolipid metabolism disorders, but the mechanism remains unclear. In this study, both a high-fat diet-induced NAFLD animal model and a cellular model exposed to free fatty acids (FFAs) were used to explore the intervention effects of EP and its mechanism in glucolipid metabolism disorders. The results revealed that a high-fat diet could induce hepatic steatosis and glucolipid metabolism disorders, along with decreased expression of IRS-1 and increased levels of K18, p-K18, p-PI3K, and p-AKT (p < 0.05). In addition, the serum K18 levels in NAFLD mice were increased. Intervention with EP significantly counteracted the high-fat diet-induced disturbances in glucose and lipid metabolism associated with NAFLD, downregulated the protein expression of hepatic K18, and decreased the levels of p-AKT, p-PI3K/PI3K, and p-AKT/AKT (p < 0.05). Knocking down K18 can directly regulate the PI3K/AKT signaling pathway. Additionally, the increases in p-PI3K/PI3K and p-AKT/AKT induced by FFAs were partially reversed after K18 was knocked down. Consequently, our findings highlight the pivotal regulatory role of K18 in modulating the high-fat diet-induced disturbances in glucolipid metabolism associated with NAFLD. Moreover, EP partially ameliorated glucolipid metabolism disorders via the K18-mediated IRS-1/PI3K/AKT/GSK3β pathway.