Yi Ping, Pang Jia, Alexander Jonathan Steven, Rivera Chantal
Molecular & Cellular Physiology, LSU Health, 1501 King Highway, Shreveport, LA, USA.
BMC Physiol. 2013 Nov 12;13:12. doi: 10.1186/1472-6793-13-12.
Postprandial lipidemia is important in the development of coronary artery disease (CAD). Consumption of a meal high in monounsaturated fat was correlated with acute impairment of endothelial function. However, the mechanisms underlying impaired endothelial function in the postprandial state have not yet been elucidated. The effects of polyunsaturated fat (corn oil) and monounsaturated fat (olive oil) on vascular dysfunction in intestinal postcapillary venules and arterioles were examined in wild-type (WT) mice, mice genetically deficient in TLR4 (TLR4-/-) and mice pre-treated with antibiotics by intravital microscopy which was performed 1.0, 1.5, 2.0, 2.5 hours after oil administration. After intravital microscopy, samples of jejunum were therefore collected to test TLR4, pNF-kB p65 and SIRT1 protein expression by western blotting.
Our findings showed that feeding mono-unsaturated olive oil or polyunsaturated corn oil promoted leukocyte and platelet trafficking in the gut microvasculature, and impaired endothelium-dependent arteriolar vasodilator responses during postprandial lipidemia. The expression of TLR4, pNF-kB p65 was significantly increased in mice gavaged with olive oil at 2 h and was significantly reduced in mice gavaged for 7 days with antibiotics and in TLR4 knockout (TLR4-/-) mice. At the same time, SIRT1 protein expression is diminished by feeding olive oil for 2 h, a phenomenon that is attenuated in mice pre-treated with antibiotics and in TLR4-/- mice. Corn oil treated mice exhibited a pattern of response similar to olive oil.
Dietary oils may be negative regulators of SIRT1 which activate the innate immune response through the endotoxin/TLR4 axis. Our findings establish a link between innate immunity (i.e. the endotoxin/TLR4 axis) and epigenetic controls mediated by SIRT1 in the genesis of diet associated vascular stress.
餐后血脂异常在冠状动脉疾病（CAD）的发生发展中具有重要意义。摄入富含单不饱和脂肪的膳食与内皮功能的急性损害相关。然而，餐后状态下内皮功能受损的潜在机制尚未阐明。通过活体显微镜检查，在野生型（WT）小鼠、基因缺失TLR4的小鼠（TLR4-/-）以及预先用抗生素处理的小鼠中，研究了多不饱和脂肪（玉米油）和单不饱和脂肪（橄榄油）对肠道毛细血管后微静脉和小动脉血管功能障碍的影响，活体显微镜检查在给予油类后1.0、1.5、2.0、2.5小时进行。活体显微镜检查后，收集空肠样本，通过蛋白质印迹法检测TLR4、磷酸化核因子κB p65和SIRT1蛋白表达。
我们的研究结果表明，喂食单不饱和橄榄油或多不饱和玉米油会促进肠道微血管中的白细胞和血小板运输，并在餐后血脂异常期间损害内皮依赖性小动脉血管舒张反应。在2小时给予橄榄油的小鼠中，TLR4、磷酸化核因子κB p65的表达显著增加，而在给予抗生素7天的小鼠和TLR4基因敲除（TLR4-/-）小鼠中显著降低。同时，喂食橄榄油2小时会使SIRT1蛋白表达减少，这一现象在预先用抗生素处理的小鼠和TLR4-/-小鼠中减弱。玉米油处理的小鼠表现出与橄榄油相似的反应模式。
膳食油类可能是SIRT1的负调节因子，其通过内毒素/TLR4轴激活先天性免疫反应。我们的研究结果在饮食相关血管应激的发生过程中，建立了先天性免疫（即内毒素/TLR4轴）与由SIRT1介导的表观遗传控制之间的联系。
