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Drug Blocks Cholesterol Absorption from the Diet: Study
Ezetimibe, also known as Zetia is the only drug that cuts the amount of cholesterol taken in from the diet rather than by blocking cholesterol's manufacture in the body.
The researchers have shown how protein known as Niemann-Pick C1-like 1 (NPC1L1) carries cholesterol into the cell.
They also show that ezetimibe bars NPC1L1's entry into the cell, thereby keeping cholesterol at bay.
In previous studies, scientists identified NPC1L1 as a critical player in cholesterol's absorption.
They also found that mice lacking this protein stop responding to ezetimibe drug. While there were clues that the drug interacts directly with the cholesterol absorption protein, the details remained unclear.
The team led by Bao-Liang Song of Shanghai Institutes for Biological Sciences now finds that cholesterol specifically encourages cells to engulf and internalize NPC1L1 in a process known as endocytosis.
In that process, part of the cell membrane pinches off to form a vesicle containing the protein.
By preventing NPC1L1's entry into the cell, the researchers showed they could dramatically reduce the amount of cholesterol taken up by cells. zetimibe accomplishes that by preventing NPC1L1 from incorporating into vesicles.
"This is a breakthrough in terms of understanding how cholesterol is absorbed," said Song
"Now we see how NPC1L1 is recycled between the cell surface and vesicles [inside the cell] and how it takes in cholesterol," Song added.
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