生物谷報道:美國華盛頓大學圣路易斯分校研究小組日前報告說,,他們發(fā)現(xiàn)人體內(nèi)一種名為CD36的蛋白質(zhì),,在腸道上部扮演著脂類吸收劑的角色。
他們認為,,這一發(fā)現(xiàn)有助于找到幫助胖人減肥的新方法,。
研究小組在發(fā)表于新一期美國《生物化學雜志》上的論文中介紹說,他們在實驗中發(fā)現(xiàn),,腸道上部會制造大量CD36,,來幫助吸收脂肪酸等。當腸道上部CD36缺失時,,腸道會啟動備份機制,,把脂類推給下部腸道去吸收。脂肪酸,、膽固醇等脂類看似只在吸收過程中多走了一段路,,但實際上區(qū)別很大。首先,,脂類需要行進至更遠處,,因此被人體吸收速度變慢,。與正常實驗鼠相比,,腸道缺乏CD36的實驗鼠吸收脂類的整體效率降低,進而影響進食,,吃得就少,。
其次,下部腸道雖然也有吸收脂類的功能,,但吸收方式有所不同,。上部腸道一般會把脂類打包成一種乳糜微粒,高效地運輸?shù)缴眢w其他部位,,CD36就在其中發(fā)揮關鍵作用,。下部腸道則把脂類分解為更小粒子,這些粒子對于人體其他組織來說不如乳糜微粒容易吸收,。
研究小組說,,他們感興趣的是,人體內(nèi)的脂類吸收和實驗鼠體內(nèi)的機制十分類似,,因此將來如果能以上部腸道為目標,,干擾CD36的吸脂過程,很可能開發(fā)出一種新穎的減肥方法。
但他們也表示,,目前的研究還處于動物實驗階段,,而且下一步面臨的一個關鍵障礙是,除了腸道上部,,CD36在人體許多地方都有分布,,如心臟、骨骼肌等,,因此開發(fā)減肥方法時,,必須保證不影響到其他組織內(nèi)CD36的正常活動,。(引自新華網(wǎng))
原始出處:
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.