Co-activating the AMPK signaling axis by low molecular weight fucoidan LF2 and fucoxanthin improves the HFD-induced metabolic syndrome in mice

Metabolic syndrome (MetS) is a pathological condition characterized by multiple metabolic abnormalities. With the global epidemic of obesity and diabetes, MetS needs more urgent treatments and interventions. Fucoxanthin (FX) and fucoidan are two important active components derived from brown algae, which have been recommended as adjunctive therapy for MetS. In this study, we found that FX and low molecular weight fucoidan fraction LF2 improved insulin resistance (IR) and enhanced insulin sensitivity in high fat diet (HFD)-induced MetS mice synergistically. LF2 and FX could ameliorate HFD-induced liver injury by reducing liver fat deposition, inflammatory response and oxidative stress. Adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling axis is a key target for LF2 and FX to improve MetS. FX and LF2 reduced adipogenesis and conversion through co-activation of AMPK and reduction of the expression of adipogenic differentiation factors. In addition, FX up-regulated the expression of uncoupling protein (UCP-1) and promoted the body's energy expenditure. However, LF2 did not significantly increase the anti-hyperlipidemic effect of FX. Collectively, this study elucidated the synergistic improvement of MetS by FX and LF2 from a molecular perspective. It also demonstrated the potential of fucoxanthin combined with fucoidan as an anti-MetS functional food.