van Greevenbroek M M, van Meer G, Erkelens D W, de Bruin T W
Department of Medicine, Academic Hospital, Utrecht University, The Netherlands.
Atherosclerosis. 1996 Mar;121(1):139-50. doi: 10.1016/0021-9150(95)05712-9.
We studied the effects of addition of physiological concentrations (0.5 mM) of fatty acids i.e., palmitic (16:0), stearic (18:0), oleic (18:1) and linoleic acid (18:2) on lipoprotein secretion by polarized Caco-2 cells. With saturated fatty acids, secreted lipoproteins were at IDL/LDL density, 1.009 < d < 1.068 g/ml. The numbers of secreted lipoproteins, expressed as secreted apolipoprotein (apo) B, were comparable to control without fatty acid (palmitic acid, 551 +/- 185; stearic acid, 629 +/- 304 and control, 504 +/- 176 ng apo B/4.7 cm2 filter). With unsaturated fatty acids, apo B containing lipoproteins were secreted at chylomicron/VLDL density (d < 1.006 g/ml). Oleic acid caused a two-fold higher secretion of apo B than control (1058 +/- 87 vs. 504 +/- 176 ng/4.7 cm2 filter, P < 0.001). The increase in apo B secretion was attributed to a specific increase in apo B-48. Unsaturated fatty acid caused a two-fold higher secretion of triglyceride than saturated fatty acids but incorporation of newly synthesized lipid into the secreted lipoproteins, measured by incorporation of a fatty acid marker, was 10- to 20-fold higher, indicating preferential translocation of unsaturated triglycerides into lipoproteins. Mixtures rich in either polyunsaturated, monounsaturated, or saturated fatty acids, resembling nutritional fat and oils, were capable of a two-fold stimulation of secretion of apo B containing triglyceride-rich lipoproteins. The triglyceride/apo B ratio in the basolateral medium was higher with the monounsaturated 'olive oil' mixture (12 250 +/- 2000 mol/mol) than with the polyunsaturated 'corn oil' mixture (7830 +/- 2480 mol/mol) and incorporation of newly synthesized lipid into the secreted lipoproteins was 1.5-fold higher as well. In conclusion, unsaturated fatty acids were most potent in stimulating the secretion of apo B by specifically increasing apo B-48 secretion. Unsaturated triglycerides, that contain mainly oleic acid, were more efficiently incorporated into lipoproteins than saturated triglycerides, suggesting preferential translocation by microsomal triglyceride transfer protein.
我们研究了添加生理浓度(0.5 mM)的脂肪酸,即棕榈酸(16:0)、硬脂酸(18:0)、油酸(18:1)和亚油酸(18:2)对极化的Caco-2细胞脂蛋白分泌的影响。对于饱和脂肪酸,分泌的脂蛋白处于IDL/LDL密度范围,1.009 < d < 1.068 g/ml。以分泌的载脂蛋白(apo)B表示的分泌脂蛋白数量与未添加脂肪酸的对照组相当(棕榈酸组,551 ± 185;硬脂酸组,629 ± 304;对照组,504 ± 176 ng apo B/4.7 cm²滤膜)。对于不饱和脂肪酸,含apo B的脂蛋白以乳糜微粒/VLDL密度(d < 1.006 g/ml)分泌。油酸导致apo B的分泌量比对照组高两倍(1058 ± 87 vs. 504 ± 176 ng/4.7 cm²滤膜,P < 0.001)。apo B分泌的增加归因于apo B-48的特异性增加。不饱和脂肪酸导致甘油三酯的分泌量比饱和脂肪酸高两倍,但通过脂肪酸标记物掺入来衡量的新合成脂质掺入分泌脂蛋白中的量要高10至20倍,这表明不饱和甘油三酯优先转运到脂蛋白中。富含多不饱和、单不饱和或饱和脂肪酸的混合物,类似于营养油脂,能够使含甘油三酯丰富的apo B脂蛋白的分泌量增加两倍。基底外侧培养基中甘油三酯/apo B的比值在单不饱和的“橄榄油”混合物(12 250 ± 2000 mol/mol)中高于多不饱和的“玉米油”混合物(7830 ± 2480 mol/mol),新合成脂质掺入分泌脂蛋白中的量也高1.5倍。总之,不饱和脂肪酸通过特异性增加apo B-48的分泌,在刺激apo B分泌方面最为有效。主要含油酸的不饱和甘油三酯比饱和甘油三酯更有效地掺入脂蛋白中,这表明微粒体甘油三酯转移蛋白优先转运不饱和甘油三酯。