Velasquez O R, Place A R, Tso P, Crissinger K D
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.
J Clin Invest. 1994 Feb;93(2):479-85. doi: 10.1172/JCI116996.
Although lipids are essential nutrients in the mammalian diet, we have shown that fatty acids are injurious to epithelial cells of developing piglet intestine during luminal perfusion. Furthermore, the intestine of young animals sustains greater injury than that of older piglets. In an effort to understand the mechanism for this developmental injury, we investigated whether changes in the chemical configuration of oleic acid would alter this damage. Mucosal permeability, as quantitated by the plasma-to-lumen clearance of 51chromium EDTA, was evaluated during luminal perfusion with oleic acid as compared with its ethyl (ethyl oleate) and glyceryl (glycerol-1-mono-oleate) esters, solubilized with taurocholic acid, in jejunum of 1-d-, 3-d-, 2-wk-, and 1-mo-old piglets. 51Chromium EDTA clearance increased significantly during oleic acid and glycerol-1-mono-oleate perfusion, but did not increase during perfusion with ethyl oleate or saline. This result was not secondary to failure of absorption of ethyl oleate, as [14C]oleic acid and ethyl [1-14C]oleate were absorbed to a similar extent. Furthermore, developing intestine was able to remove the ethyl group and then re-esterify the fatty acid to form triacyglycerol. These studies indicate that oleic acid-induced mucosal injury can be abolished when the carboxylic group of the fatty acid is esterified with an ethyl, but not a glycerol, group. Since the ethyl ester is also absorbed and metabolized similarly to the free fatty acid, this may provide a means of supplying long-chain fatty acids to developing intestine without causing mucosal damage.
尽管脂质是哺乳动物饮食中的必需营养素,但我们已经表明,在肠腔灌注期间,脂肪酸对发育中的仔猪肠道上皮细胞具有损害作用。此外,幼龄动物的肠道比大龄仔猪的肠道遭受的损伤更大。为了了解这种发育性损伤的机制,我们研究了油酸化学结构的变化是否会改变这种损伤。在用牛磺胆酸溶解的油酸及其乙酯(油酸乙酯)和甘油酯(甘油-1-单油酸酯)对1日龄、3日龄、2周龄和1月龄仔猪的空肠进行肠腔灌注期间,通过51铬乙二胺四乙酸的血浆到肠腔清除率来定量评估黏膜通透性。在油酸和甘油-1-单油酸酯灌注期间,51铬乙二胺四乙酸清除率显著增加,但在油酸乙酯或生理盐水灌注期间没有增加。这一结果并非由于油酸乙酯吸收失败所致,因为[14C]油酸和[1-14C]油酸乙酯的吸收程度相似。此外,发育中的肠道能够去除乙基,然后将脂肪酸重新酯化形成三酰甘油。这些研究表明,当脂肪酸的羧基与乙基而非甘油基酯化时,油酸诱导的黏膜损伤可以消除。由于乙酯的吸收和代谢与游离脂肪酸相似,这可能提供了一种在不引起黏膜损伤的情况下向发育中的肠道供应长链脂肪酸的方法。