Abstract：
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.
摘要：
脂蛋白脂肪酶（LPL）水解循环甘油三酯（TG），在白色脂肪组织（WAT）中释放脂肪酸（FA）并促进脂质储存。然而,调节脂肪LPL的机制及其与高甘油三酯血症发展的关系尚不清楚。来自肥胖人类的WAT表现出高PAR2表达，与LPL基因呈负相关。LPL表达降低也与血浆TG水平升高呈负相关。提示脂肪PAR2可能通过下调LPL来调节高甘油三酯血症。在老鼠身上,衰老和高棕榈酸饮食（PD）增加了WAT中PAR2的表达，这与高水平的巨噬细胞迁移抑制因子（MIF）有关。MIF通过与CXCR2/4受体结合并抑制Akt磷酸化而下调脂肪细胞中LPL的表达和活性。在MIF过表达模型中,高循环MIF水平抑制脂肪LPL，这种抑制与血浆TG增加有关，但与FA无关。PD喂食后，脂肪LPL表达和活性显著降低，这种减少在Par2-/-小鼠中被逆转。重组MIF输注恢复了Par2-/-小鼠的高血浆MIF水平，LPL水平降低，脂肪细胞脂质储存减弱，导致高甘油三酯血症。这些数据共同表明PAR2/MIF对脂肪LPL的下调可能有助于高甘油三酯血症的发展。
