Cholesterol – a waxy, fatty substance found in every cell in the body – is made mainly from acetyl-coenzyme A (or acetyl-CoA). It’s a fundamental compound at the crossroad of many metabolic pathways, including carbohydrate and amino-acid metabolism. An enzyme called HMG-CoA reductase is involved in these metabolic processes.
The liver is an important hub of cholesterol metabolism in the body. This organ balances the daily requirements for cholesterol by sensing the amount the body contains.
The liver receives dietary and biliary cholesterol by taking in the remnants of chylomicrons – large particles that carry dietary fats through the bloodstream and which contain some cholesterol. It can also take in LDL cholesterol from the blood, and does this by expressing low density lipoprotein (LDL) receptors when necessary. The liver can also draw on a stored form of cholesterol in its cells.
The liver exports cholesterol directly into bile, but also indirectly: it secretes bile acids made from cholesterol into the bile. The other form of export is as very-low-density lipoprotein (VLDL), which circulate in the bloodstream.
When there’s too little cholesterol in the liver, there’s a programmed response to turn on HMGCoA reductase as well as LDL receptors to make good the deficit. When there’s an excess of cholesterol in the liver, as in the case of a very cholesterol-rich diet, these two processes are switched off.
The switching off of LDL receptors means less LDL is removed from the blood. As a result, the blood LDL cholesterol level rises by small amounts over a few weeks to reach a new level. This is when the liver achieves a new, balanced state.
Apart from making new cholesterol, the body also recycles the cholesterol used for bile production. Between 92% and 97% of the cholesterol in bile is reabsorbed from the gut and recycled back to the liver, where it can be reused.
About 20% of the cholesterol in your body comes from the food you eat. The efficiency of the absorption of cholesterol varies among people and thus the response to diet can also differ. In some people, cholesterol levels remain high, regardless of dietary intake. This is usually due to genetic abnormalities in the LDL receptor. For these people, limiting fats in the diet may have very little influence on cholesterol levels. But dietary fats are transported through the blood after meals, which means they may still contribute to risk.
Reviewed by Prof David Marais, FCP(SA), Head of Lipidology at Groote Schuur Hospital and the University of Cape Town. January 2018.