生物谷报道:美国华盛顿大学圣路易斯分校研究小组日前报告说,他们发现人体内一种名为CD36的蛋白质,在肠道上部扮演着脂类吸收剂的角色。
他们认为,这一发现有助于找到帮助胖人减肥的新方法。
研究小组在发表于新一期美国《生物化学杂志》上的论文中介绍说,他们在实验中发现,肠道上部会制造大量CD36,来帮助吸收脂肪酸等。当肠道上部CD36缺失时,肠道会启动备份机制,把脂类推给下部肠道去吸收。脂肪酸、胆固醇等脂类看似只在吸收过程中多走了一段路,但实际上区别很大。首先,脂类需要行进至更远处,因此被人体吸收速度变慢。与正常实验鼠相比,肠道缺乏CD36的实验鼠吸收脂类的整体效率降低,进而影响进食,吃得就少。
其次,下部肠道虽然也有吸收脂类的功能,但吸收方式有所不同。上部肠道一般会把脂类打包成一种乳糜微粒,高效地运输到身体其他部位,CD36就在其中发挥关键作用。下部肠道则把脂类分解为更小粒子,这些粒子对于人体其他组织来说不如乳糜微粒容易吸收。
研究小组说,他们感兴趣的是,人体内的脂类吸收和实验鼠体内的机制十分类似,因此将来如果能以上部肠道为目标,干扰CD36的吸脂过程,很可能开发出一种新颖的减肥方法。
但他们也表示,目前的研究还处于动物实验阶段,而且下一步面临的一个关键障碍是,除了肠道上部,CD36在人体许多地方都有分布,如心脏、骨骼肌等,因此开发减肥方法时,必须保证不影响到其他组织内CD36的正常活动。(引自新华网)
原始出处:
J. Biol. Chem., Vol. 282, Issue 27, 19493-19501, July 6, 2007
CD36 Is Important for Fatty Acid and Cholesterol Uptake by the Proximal but Not Distal Intestine*
Fatiha Nassir1, Brody Wilson, Xianlin Han, Richard W. Gross, and Nada A. Abumrad2
From the Department of Medicine, Divisions of Nutritional Science and Bioorganic Chemistry and Molecular Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110
CD36, a membrane protein that facilitates fatty acid uptake, is highly expressed in the intestine on the luminal surface of enterocytes. Cd36 null (Cd36–/–) mice exhibit impaired chylomicron secretion but no overall lipid absorption defect. Because chylomicron production is most efficient proximally we examined whether CD36 function is important for proximal lipid absorption. CD36 levels followed a steep decreasing gradient along three equal-length, proximal to distal intestinal segments (S1–S3). Enterocytes isolated from the small intestines of Cd36–/– mice, when compared with wild type counterparts, exhibited reduced uptake of fatty acid (50%) and cholesterol (60%) in S1. The high affinity fatty acid uptake component was missing in Cd36–/– cells. Fatty acid incorporation into triglyceride and triglyceride secretion were also reduced in Cd36–/– S1 enterocytes. In vivo, proximal absorption was monitored using mass spectrometry from oleic acid enrichment of S1 lipids, 90 min (active absorption) and 5 h (steady state) after intragastric olive oil (70% triolein). Oleate enrichment was 50% reduced at 90 min in Cd36–/– tissue consistent with defective uptake whereas no differences were measured at 5 h. In Cd36–/– S1, mRNA for L-fabp, Dgat1, and apoA-IV was reduced. Protein levels for FATP4, SR-BI, and NPC1L1 were similar, whereas those for apoB48 and apoA-IV were significantly lower. A large increase in NPC1L1 was observed in Cd36–/– S2 and S3. The findings support the role of CD36 in proximal absorption of dietary fatty acid and cholesterol for optimal chylomicron formation, whereas CD36-independent mechanisms predominate in distal segments.