Hansen Gert H, Rasmussen Karina, Niels-Christiansen Lise-Lotte, Danielsen E Michael
Department of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen, Denmark.
Mol Membr Biol. 2011 Feb;28(2):136-44. doi: 10.3109/09687688.2010.542552. Epub 2010 Dec 17.
Free fatty acids released during intralumenal digestion of dietary fat must pass through the enterocyte brush border membrane before triacylglycerol reassembly and subsequent chylomicron delivery to the lymph system. In the present work fluorescent BODIPY fatty acid analogs were used to study this membrane passage in organ cultured intestinal mucosal explants. We found that in addition to a rapid uptake into the cytoplasm, a fraction of the fatty acid analogs were inserted directly into the brush border membrane. Furthermore, a brief exposure of microvillar membrane vesicles to a fat mixture mimicking a physiological solution of dietary mixed micelles, rearranged the lipid raft microdomain organization of the membranes. Thus, the fat mixture generated a low-density subpopulation of microvillar detergent resistant membranes (DRMs) highly enriched in alkaline phosphatase (AP). Since this GPI-linked enzyme is the membrane protein in the brush border with the highest affinity for lipid rafts, this implies that free fatty acids selectively insert stably into these membrane microdomains. We have previously shown that absorption of dietary lipids transiently induce a selective endocytosis of AP from the brush border, and from work by others it is known that fat absorption is accompanied by a rise in serum AP and secretion of surfactant-like particles from enterocytes. We propose that these physiological processes may be triggered by the sequestering of dietary free fatty acids in lipid raft microdomains of the brush border.
膳食脂肪在肠腔内消化过程中释放的游离脂肪酸，在三酰甘油重新组装以及随后乳糜微粒输送至淋巴系统之前，必须穿过肠上皮细胞刷状缘膜。在本研究中，使用荧光BODIPY脂肪酸类似物来研究器官培养的肠黏膜外植体中的这种膜转运过程。我们发现，除了快速摄取到细胞质中之外，一部分脂肪酸类似物还直接插入到刷状缘膜中。此外，将微绒毛膜囊泡短暂暴露于模拟膳食混合微团生理溶液的脂肪混合物中，会重新排列膜的脂筏微区组织。因此，该脂肪混合物产生了一个低密度的微绒毛抗去污剂膜（DRM）亚群，其富含碱性磷酸酶（AP）。由于这种糖基磷脂酰肌醇连接的酶是刷状缘中对脂筏亲和力最高的膜蛋白，这意味着游离脂肪酸选择性地稳定插入这些膜微区。我们之前已经表明，膳食脂质的吸收会短暂诱导刷状缘AP的选择性内吞作用，并且从其他人的研究中可知，脂肪吸收伴随着血清AP的升高以及肠上皮细胞表面活性剂样颗粒的分泌。我们提出，这些生理过程可能是由膳食游离脂肪酸在刷状缘脂筏微区中的隔离所触发的。
