Chung B H, Hennig B, Cho B H, Darnell B E
Department of Medicine, University of Alabama at Birmingham, 35294-0012, USA.
Atherosclerosis. 1998 Dec;141(2):321-32. doi: 10.1016/s0021-9150(98)00168-3.
Ingestion of a meal increases plasma levels of triglyceride (TG)-rich lipoproteins through the secretion of intestine-derived chylomcirons and liver-derived very low density lipoproteins (VLDL). We have determined the effects of the fat composition of a single meal on the composition of TG in TG-rich lipoproteins (VLDL + chylomicrons) and circulating and lipolytically-releasable free fatty acids (FFA) in postprandial (PP) plasma and on the cytotoxic potencies of the lipolytically-released FFA to cultured arterial wall cells. PP lipemia was induced by feeding fasted normolipidemic human subjects with a meal rich in saturated fat (SF) and another meal rich in polyunsaturated fat (PUF), or vice versa; each meal provided 65% of energy as fat, and polyunsaturated to saturated fatty acid ratios (P/S) of the SF and PUF in the meals were 0.40 and 2.49, respectively. The mean P/S of TG in TG-rich lipoproteins (1.43) and circulating FFA (1.46) in 4 h PP plasma of PUF were significantly higher than those in PP plasma of SF (0.44 and 0.59, respectively) in fasting plasma (0.52 and 0.53, respectively). In vitro lipolysis of fasting and PP serum by purified bovine milk lipoprotein lipase (LpL) resulted in a marked (8.8-12.3-fold) increase in the serum FFA level. The P/S of serum FFA in postlipolysis fasting and PP serum were consistently higher than that of FFA or that of TG associated with TG-rich lipoproteins in prelipolysis fasting and PP serum, indicating that polyunsaturated TG in VLDL and/or chylomicrons is more susceptible than saturated TG to lipolysis. When postlipolysis serum was interacted with cultured endothelial cells and mouse peritoneal macrophages (MPM), the lipolytically-released FFA in PP serum of SF and PUF disrupted the barrier function of endothelial cells and were cytotoxic to cultured MPM; FFA in postlipolysis fasting serum was not cytotoxic. FFA in postlipolysis PP serum of PUF were consistently more potent than that in postlipolysis PP serum of SF. Further study showed that all long-chain monounsaturated FFA and polyunsaturated FFA, but not saturated FFA, incorporated into lipoproteins (LDL) were cytotoxic to cultured MPM. In conclusion, despite the generally well-accepted belief that SF is more atherogenic than PUF, the present study provides in vitro evidence that the lipolytic remnant products of TG-rich lipoproteins produced after a meal rich in PUF are more injurious to arterial wall cells than those produced after a meal rich in SF.
进食一顿饭会通过分泌肠道来源的乳糜微粒和肝脏来源的极低密度脂蛋白(VLDL)来提高富含甘油三酯(TG)的脂蛋白的血浆水平。我们已经确定了一顿饭的脂肪组成对富含TG的脂蛋白(VLDL + 乳糜微粒)中TG的组成、餐后(PP)血浆中循环的和可通过脂解释放的游离脂肪酸(FFA)的影响,以及脂解释放的FFA对培养的动脉壁细胞的细胞毒性。通过给空腹的血脂正常的人类受试者喂食富含饱和脂肪(SF)的一顿饭和另一顿富含多不饱和脂肪(PUF)的饭,或者反之亦然,来诱导PP脂血症;每顿饭提供65%的能量作为脂肪,饭中SF和PUF的多不饱和脂肪酸与饱和脂肪酸的比例(P/S)分别为0.40和2.49。PUF组4小时PP血浆中富含TG的脂蛋白中TG的平均P/S(1.43)和循环FFA的平均P/S(1.46)显著高于SF组PP血浆中的(分别为0.44和0.59),而空腹血浆中的(分别为0.52和0.53)。用纯化的牛乳脂蛋白脂肪酶(LpL)对空腹和PP血清进行体外脂解导致血清FFA水平显著升高(8.8 - 12.3倍)。脂解后空腹和PP血清中FFA的P/S始终高于脂解前空腹和PP血清中FFA或与富含TG的脂蛋白相关的TG的P/S,这表明VLDL和/或乳糜微粒中的多不饱和TG比饱和TG更容易被脂解。当脂解后的血清与培养的内皮细胞和小鼠腹腔巨噬细胞(MPM)相互作用时,SF和PUF的PP血清中脂解释放的FFA破坏了内皮细胞的屏障功能,并且对培养的MPM具有细胞毒性;脂解后空腹血清中的FFA没有细胞毒性。PUF的脂解后PP血清中的FFA始终比SF的脂解后PP血清中的FFA毒性更强。进一步的研究表明,所有掺入脂蛋白(LDL)的长链单不饱和FFA和多不饱和FFA,但不是饱和FFA,对培养的MPM具有细胞毒性。总之,尽管人们普遍认为SF比PUF更具动脉粥样硬化性,但本研究提供了体外证据,表明富含PUF的一顿饭后产生的富含TG的脂蛋白的脂解残余产物比富含SF的一顿饭后产生的对动脉壁细胞更具伤害性。