Hannah J S, Yamane K, Berlin E, Howard B V
Medlantic Research Institute, Washington, DC 20010, USA.
Metabolism. 1995 Nov;44(11):1428-34. doi: 10.1016/0026-0495(95)90142-6.
Low-density lipoprotein (LDL) receptor binding is the initial step in receptor-mediated clearance. Dietary fat composition is known to affect LDL clearance, but the mechanism of the effect is unknown. We have examined the effects of altered membrane fatty acid composition, as might occur when specific dietary fats are consumed, on LDL binding using a Chinese hamster ovary (CHO) line that constitutively expresses the human LDL receptor. Binding of pooled human LDL to its receptor was compared in cells enriched with various fatty acids. Binding affinity was greater (lower Kd) for cells grown in 16:0-, 18:0-, or 18:1-enriched media than for those grown in 18:2 (P < .0001). The apparent receptor number (Bmax) was lower for cells enriched in saturated fatty acids and 18:1. Fluidity was assessed by measuring diphenylhexatriene (DPH) fluorescence anisotropy (rs). Cells enriched in 18:1 or 18:2 were the most fluid (P < .003). The correlation between binding and fluidity (r = .24, P = .27) was weak and did not appear to explain the effects of fatty acid modification on LDL receptor binding. Thus, it appears that cellular enrichment in 16:0, 18:0, and 18:1 increases binding affinity by affecting properties other than membrane fluidity. Changes in Bmax may also contribute to the observed differences in LDL binding.
低密度脂蛋白（LDL）受体结合是受体介导清除的起始步骤。已知膳食脂肪组成会影响LDL清除，但这种影响的机制尚不清楚。我们使用组成型表达人LDL受体的中国仓鼠卵巢（CHO）细胞系，研究了食用特定膳食脂肪时可能发生的膜脂肪酸组成改变对LDL结合的影响。在富含各种脂肪酸的细胞中比较了混合人LDL与其受体的结合。在富含16:0、18:0或18:1的培养基中生长的细胞，其结合亲和力高于在富含18:2的培养基中生长的细胞（P <.0001）。富含饱和脂肪酸和18:1的细胞的表观受体数量（Bmax）较低。通过测量二苯基己三烯（DPH）荧光各向异性（rs）评估流动性。富含18:1或18:2的细胞流动性最高（P <.003）。结合与流动性之间的相关性较弱（r =.24，P =.27），似乎无法解释脂肪酸修饰对LDL受体结合的影响。因此，似乎细胞中16:0、18:0和18:1的富集通过影响膜流动性以外的特性增加了结合亲和力。Bmax的变化也可能导致观察到的LDL结合差异。
