How cholesterol in our diet is absorbed into our cells

Researchers have discovered the mechanism by which cholesterol in our diet is absorbed into our cells.

This discovery, which has just been published in the journal Science opens up new opportunities for therapeutic intervention to control cholesterol uptake that could complement other therapies and potentially save lives.

The research has shown that two proteins (called Aster B and Aster C) play a key role in transporting cholesterol from the membrane of the cells lining our intestine to the internal compartment where it is modified prior to circulation.

The researchers used their expertise to reveal how Ezetimibe, a cholesterol lowering drug, blocks the ability of Aster B and C to transport cholesterol.

Cholesterol is a natural fatty substance found in the blood. Produced in the liver, it is also found in some of the foods we eat such as red meat and dairy products. Frying our food can also add to cholesterol in our diet.

Although we need cholesterol in our bodies to function, having too much (high cholesterol) can clog our arteries and cause health problems such as heart disease.

The researchers said: “If we can prevent some cholesterol from being absorbed into our cells, we may ultimately be able to prevent individuals from having high cholesterol and cut down their risks of heart attack and stroke and therefore potentially save lives.

Niemann-Pick C1 Like 1 (NPC1L1), the target of the hypocholesterolemic drug ezetimibe (EZ), facilitates the deposition of dietary cholesterol from the gut lumen into the apical plasma membrane (PM) of enterocytes. Subsequently, cholesterol moves to the endoplasmic reticulum (ER) where it is esterified by ACAT2. Cholesterol ester is packaged into chylomicrons for release into the circulation and delivery to tissues. How cholesterol moves from the brush border of enterocytes to the ER, however, has been a longstanding question.

NPC1L1 mediates the deposition of dietary cholesterol at the brush border, thus recruiting Asters to form PM-ER contact sites. Asters subsequently facilitate the nonvesicular movement of cholesterol to ER for esterification.

Deletion of Asters causes ER sterol depletion, activation of SREBP2, production of chylomicrons depleted of cholesterol esters, and reduced systemic cholesterol burden. 

https://www.science.org/doi/10.1126/science.adf0966

Edited

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