TY - JOUR
T1 - Dietary free fatty acids form alkaline phosphatase-enriched microdomains in the intestinal brush border membrane
AU - Hansen, Gert H
AU - Rasmussen, Karina
AU - Niels-Christiansen, Lise-Lotte
AU - Danielsen, E Michael
PY - 2011/2/1
Y1 - 2011/2/1
N2 - 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.
AB - 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.
KW - Alkaline Phosphatase
KW - Digestion
KW - Electrophoresis, Polyacrylamide Gel
KW - Fatty Acids, Nonesterified
KW - Food
KW - Humans
KW - Intestinal Mucosa
KW - Lipid Bilayers
KW - Membrane Microdomains
KW - Microscopy, Electron
KW - Microscopy, Fluorescence
KW - Microvilli
KW - Organ Culture Techniques
U2 - 10.3109/09687688.2010.542552
DO - 10.3109/09687688.2010.542552
M3 - Journal article
C2 - 21166483
SN - 0968-7688
VL - 28
SP - 136
EP - 144
JO - Molecular Membrane Biology
JF - Molecular Membrane Biology
IS - 2
ER -