Intestinal lipids and lipoproteins in the human fetus: modulation by epidermal growth factor.

Intestinal lipids and lipoproteins in the human fetus: modulation by epidermal growth factor.
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DOI:
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发表时间:
1992-11
影响因子:
6.5
通讯作者:
Emile Levy;Louise Thibault;Daniel M6nard
Emile Levy;Louise Thibault;Daniel M6nard
中科院分区:
生物学2区
文献类型:
--
作者:
Emile Levy;Louise Thibault;Daniel M6nard

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本研究的目的是:第一,检查人胎儿肠(17-20周)的能力,将脂肪酸酯化脂质;第二,研究体外脂蛋白合成和分泌的胎儿外植体,以及表皮生长因子(EGF)对这些过程的影响。将培养的胎儿空肠外植体在Leibovitz培养基中与[14 C]油酸盐孵育42小时。甘油三酯(TG)和磷脂(PL)是主要的标记产物。而TG占主要(80%)在培养基中,PL占总组织脂质的50%以上。PL中超过60%的放射性与磷脂酰胆碱相关。在胆固醇酯级分中也回收了一些标记(< 5%)。新合成的酯化脂质在培养基中的积累和脂蛋白在基底外侧膜区域和细胞间隙中的存在证明了主动胞吐作用。新合成的脂质以d < 0.97 g/ml(51.2%)和d < 1.21 g/ml(39.3%)的脂蛋白为主,其余为d < 1.006 g/ml(9.8%)和1.063 g/ml(5.6%)的脂蛋白。脂蛋白分泌也有类似的趋势。d < 0.97 g/ml组分(30,653 +/-4,122 dpm/mg蛋白质)的合成显著大于1.006 g/ml组分(5,897 +/-1,734),P < 0.005。d < 0.97 μ g/ml的颗粒向培养基中的分泌也比d < 1.006 μ g/ml的组分高5倍(P < 0.01)。在培养基中加入EGF(25、50和100 ng/ml)可显著提高d < 0.97 g/ml的脂蛋白分泌(25-40%),并降低d <1.006 g/ml和1.063 g/ml的组分产量。这些脂蛋白组分的脂质组成从来没有改变EGF的存在下,这表明脂蛋白颗粒的数量,而不是大小,被修改的生长因子。目前的研究结果提供了第一个证据表明,人类胎儿肠道有能力制定脂蛋白组分的运输新合成的脂质。此外,我们的数据表明,EGF,目前在唾液,羊水和胆汁中的显着数量,可以调节释放富含TG的脂蛋白的胎儿肠外植体。
The aim of the present investigation was first, to examine the ability of human fetal intestine (17-20 wk) to incorporate fatty acid into esterified lipids; and second, to study in vitro lipoprotein synthesis and secretion by fetal explants, as well as the effect of epidermal growth factor (EGF) on these processes. Cultured fetal jejunal explants were incubated in Leibovitz medium for 42 h with [14C]oleate. Both triglycerides (TG) and phospholipids (PL) were the major labeled products. Whereas TG were predominant (80%) in the culture medium, PL accounted for more than 50% of total tissue lipids. More than 60% of the radioactivity in PL was associated with phosphatidylcholine. Some labeling (< 5%) was also recovered in the cholesteryl ester fraction. Active exocytosis was demonstrated by the accumulation of newly synthesized esterified lipids in the medium and the presence of lipoproteins in the basolateral membrane region and intercellular spaces. Most of the newly synthesized lipids were found in lipoproteins of d < 0.97 g/ml (51.2%) and d < 1.21 g/ml (39.3%), whereas the rest were recovered in d < 1.006 g/ml (9.8%) and 1.063 g/ml (5.6%). A similar trend characterized the lipoprotein secretion. The synthesis of the d < 0.97 g/ml fraction (30,653 +/- 4,122 dpm/mg protein) was significantly greater than the 1.006 g/ml fraction (5,897 +/- 1,734), P < 0.005. The secretion of d < 0.97 g/ml particles into the medium was also five fold higher than that of the d < 1.006 g/ml fraction (P < 0.01). The addition of EGF to the culture medium (25, 50, and 100 ng/ml) significantly enhanced the d < 0.97 g/ml lipoprotein secretion (25-40%) and decreased the d 1.006 g/ml and 1.063 g/ml fraction output. The lipid composition of these lipoprotein fractions was never altered by the presence of EGF, suggesting that the number of lipoprotein particles, rather than size, was modified by the growth factor. The present findings provide the first evidence that the human fetal intestine has the capacity to elaborate lipoprotein fractions for the transport of newly synthesized lipids. Furthermore, our data suggest that EGF, present in significant quantity in saliva, amniotic fluid, and bile, can modulate the release of TG-rich lipoproteins by fetal intestinal explants.