The liver plays a key role in the regulation of cholesterol levels:
Certainly LDL transport cholesterol from the liver to the extra hepatic tissues, but we should not forget that most of the LDL receptors are located in the liver; consequently around 80 % of the LDL that is formed in blood as a result of the transformation of VLDL to IDL to LDL, is actually catabolized by the liver, and barely around 20 % is used by the extra hepatic tissues (anyway, this 20 % is enough for producing atherosclerosis in case of an excess of cholesterol!).
The importance of the liver in the regulation of cholesterolemia in fact, depends on different factors:
1.- As described before, the liver has most of LDL receptors.
2.- Hepatocytes are the cells with a higher level of HMGCoA reductase, the regulatory enzyme of cholesterol synthesis.
3. – The liver is the organ where cholesterol can be excreted from the body, as bile acids or as cholesterol associated to the bile acids.
The excretion of cholesterol through the bile requires the conversion of cholesterol to a more polar compound: cholesterol loses carbons in its lateral chain and is dihidroxylated, forming cholic and chenodeoxycholic acids, the primary bile acids.
The solubility of these primary bile acids increases when they are conjugated to glycine and taurine, to form glycocholic and chenodeoxycholic acids. In the alkaline environment that predominates in the common duct and in the duodenum, as a result of pancreatic secretions, these acids are ionized and are called bile salts.
Bile acids are eliminated to the small intestine where they are transformed by the intestinal flora and become secondary bile acids; deoxycholic and lithocholic acids or their corresponding salts.
Bile acids perform important functions in our body:
1. – They are the main way in which cholesterol can be disposed from the body.
2. – Since they are more hydrosoluble than their precursor cholesterol, they prevent the accumulation and precipitation of cholesterol in the gall bladder.
3. – They are emulsifying agents for the digestion of fats.
4. – They facilitate the absorption of liposoluble vitamins.
Since the quantity of bile acids that we require everyday for digestion is 50 to 100 times higher than the quantity of cholesterol that is synthesized or is captured by the liver (15-30 g vs. 0.3 -0.5 g), bile salts are reabsorbed so they are excreted in very small amounts through the feces: just a quantity similar to the quantity of cholesterol that is captured and synthesized in the liver. The process of reabsortion of the bile acids is called the enterohepatic circulation of bile acids.
Cholestyramine and Colestipol are non absorbable resins used in the treatment of hypercholesterolemia. These resins combine to bile acids preventing their intestinal reabsorption and therefore the body should increase the transformation of cholesterol into bile acids. This decrease in intracellular cholesterol in turn stimulates the synthesis of LDL receptors, and consequently, increases the liver capture of LDL, decreasing the concentration of LDL cholesterol in blood.