Context: Fucoidan, a sulphated polysaccharide extracted from brown algae [Fucus vesiculosus Linn. (Fucaceae)], has multiple biological activities. Objective: The effects of fucoidan on Ca²⁺ responses of rat neurons and its probable mechanisms with focus on glutamate receptors were examined. Materials and methods: The neurons isolated from the cortex and hippocampi of Wistar rats in postnatal day 1 were employed. The intracellular Ca²⁺ responses triggered by various stimuli were measured in vitro by Fura-2/AM. Fucoidan at 0.5 mg/mL or 1.5 mg/mL was applied for 3 min to determine its effects on Ca²⁺ responses. RT-PCR was used to determine the mRNA expression of neuron receptors treated with fucoidan at 0.5 mg/mL for 3 h. Results: The Ca²⁺ responses induced by NMDA were 100% suppressed by fucoidan, and those induced by Bay K8644 90% in the cortical neurons. However, fucoidan has no significant effect on the Ca²⁺ responses of cortical neurons induced by AMPA or quisqualate. Meanwhile, the Ca²⁺ responses of hippocampal neurons induced by glutamate, ACPD or adrenaline, showed only a slight decrease following fucoidan treatment. RT-PCR assays of cortical and hippocampal neurons showed that fucoidan treatment significantly decreased the mRNA expression of NMDA-NR1 receptor and the primer pair for l-type Ca²⁺ channels, PR1/PR2. Discussion and conclusions: Our data indicate that fucoidan suppresses the intracellular Ca²⁺ responses by selectively inhibiting NMDA receptors in cortical neurons and l-type Ca²⁺ channels in hippocampal neurons. A wide spectrum of fucoidan binding to cell membrane may be useful for designing a general purpose drug in future.

Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs), releasing fatty acids (FA) and promoting lipid storage in white adipose tissue (WAT). However, the mechanisms regulating adipose LPL and its relationship with the development of hypertriglyceridemia are largely unknown. WAT from obese humans exhibited high PAR2 expression, which was inversely correlated with the LPL gene. Decreased LPL expression was also inversely correlated with elevated plasma TG levels, suggesting that adipose PAR2 might regulate hypertriglyceridemia by downregulating LPL. In mice, aging and high palmitic acid diet (PD) increased PAR2 expression in WAT, which was associated with a high level of macrophage migration inhibitory factor (MIF). MIF downregulated LPL expression and activity in adipocytes by binding with CXCR2/4 receptors and inhibiting Akt phosphorylation. In a MIF overexpression model, high-circulating MIF levels suppressed adipose LPL, and this suppression was associated with increased plasma TGs but not FA. Following PD feeding, adipose LPL expression and activity were significantly reduced, and this reduction was reversed in Par2 ^–/– mice. Recombinant MIF infusion restored high plasma MIF levels in Par2 ^–/– mice, and the levels decreased LPL and attenuated adipocyte lipid storage, leading to hypertriglyceridemia. These data collectively suggest that downregulation of adipose LPL by PAR2/MIF may contribute to the development of hypertriglyceridemia.