INTESTINAL METABOLISM OF PLASMA-FREE FATTY-ACIDS - INTRACELLULAR COMPARTMENTATION AND MECHANISMS OF CONTROL

INTESTINAL METABOLISM OF PLASMA-FREE FATTY-ACIDS - INTRACELLULAR COMPARTMENTATION AND MECHANISMS OF CONTROL
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DOI:
10.1172/jci107991
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发表时间:
1975-01-01
影响因子:
15.9
通讯作者:
OCKNER, RK
OCKNER, RK
中科院分区:
医学1区
文献类型:
--
作者:
GANGL, A;OCKNER, RK

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肠粘膜中的脂肪酸代谢主要在脂质吸收方面进行了检查。由于早期的研究表明血浆游离脂肪酸(FFA)的肠道利用,我们研究了大鼠血浆FFA的粘膜代谢。静脉注射[14C]棕榈酸盐后2分钟,粘液素放射性(给药的1%)最大。在粘膜14C中,42%在水溶性代谢物中,包括CO2和酮酸,28%在磷脂中,只有16%在甘油三酯中。粘膜甘油三酯脂肪酸(TGFA)的比活性是血清TGFA的11倍,证实原位合成。双同位素实验表明,从管腔和血浆同时进入粘膜的脂肪酸的代谢存在显着差异。而管腔脂肪酸主要酯化甘油三酯,血浆游离脂肪酸优先氧化,并纳入磷脂。隐窝与绒毛没有区别,表明血浆FFA的肠代谢与其进入上皮细胞的位点有关。葡萄糖给药对静脉注射[14C]棕榈酸酯的粘液糖代谢影响极小。然而,十二指肠内等热量乙醇可抑制60%的FFA粘膜氧化,并使其与甘油三酯的结合增加近两倍。在脂质吸收过程中,血浆FFA的粘膜吸收增加了一倍,并纳入肠淋巴甘油三酯增加了6倍。这些研究证明了肠上皮细胞内脂肪酸的区室化。与吸收的管腔脂肪酸相反,空腹状态下的血浆FFA既是能量来源,也是合成组织磷脂的底物。空腹血浆游离脂肪酸对粘膜和淋巴甘油三酯的贡献很小,但在乙醇给药和脂肪吸收过程中会增加。
Fatty acid metabolism in intestinal mucosa has been examined primarily in regard to lipid absorption. Since earlier studies suggested intestinal utilization of plasma free fatty acids (FFA), we investigated mucosal metabolism of plasma FFA in rats. Mucosal radioactivity (1 per cent of administered) was maximal 2 min after i.v. [14C]palmitate. Of mucosal 14C, 42 percent was in water-soluble metabolites, including CO2 and ketoacids, 28 percent in phospholipids, and only 16 per cent in triglycerides. The specific activity of mucosal triglyceride fatty acids (TGFA) was 11 times that of serum TGFA, confirming in situ synthesis. Double isotope experiments showed marked differences in the metabolism of fatty acids entering mucosa simultaneously from lumen and plasma. Whereas luminal fatty acids were chiefly esterified to triglyceride, plasma FFA were preferentially oxidized and incorporated into phospholipids. Crypts did not differ from villi, indicating that intestinal metabolism of plasma FFA is related to their site of entry into epithelial cells. Mucosal metabolism of i.v. [14C]palmitate was minimally affected by glucose administration. However, intraduodenal isocaloric ethanol inhibited mucosal oxidation of FFA by 60 per cent, and increased incorporation into triglycerides nearly twofold. During lipid absorption, mucosal uptake of plasma FFA doubled and incorporation into intestinal lymph triglycerides was increased sixfold. These studies demonstrate an intracellular compartmentation of fatty acids in the intestinal epithelium. In contrast to absorbed luminal fatty acids, plasma FFA in the fasting state are both an energy source and a substrate for the synthesis of tissue phospholipid. The fasting contribution of plasma FFA to mucosal and lymph triglyceride is minimal, but it increases during ethanol administration and fat absorption.