Low molecular weight fucoidan fraction LF2 improves metabolic syndrome via up-regulating PI3K-AKT-mTOR axis and increasing the abundance of Akkermansia muciniphila in the gut microbiota

Metabolic syndrome (MetS) is a pathological condition of a variety of metabolic abnormalities, which requires more urgent treatment and intervention. Fucoidan has been recommended as a supplement for health enhancement and disease management. Here, we first propose that the beneficial effect of low molecular weight fucoidan fraction LF2 in regulating metabolic syndrome induced by high-fat diet is similar to that of metformin, in terms of molecular mechanism and gut microbiota. The study found that LF2 significantly reduces fasting blood glucose, enhances insulin sensitivity and restores insulin homeostasis and lipid homeostasis. Moreover, LF2 reduced liver oxidative stress and inflammation, and improved hepatocyte steatosis. To decipher the mechanism behind this therapeutic effect, both the molecular mechanisms and gut microbiota were further analyzed. LF2 inhibited the activation of PI3K-Akt-mTOR axis and decreased the expression of SREBP-1c and PPAR gamma in liver. Interestingly, we found that LF2 and metformin have similar effects on gut microbiota, increasing the proportion of Verrucomicrobia and enriching the abundance of Akkermansia muciniphila, which is beneficial to host health. Collectively, our research clarifies the new application of fucoidan as a functional food for anti-MetS, and provides a new insight for fucoidan to exert systemic therapeutic effects from the perspective of molecular mechanism and gut microbiota.