Dietary cholesterol represents only about one-third of our total cholesterol needs, remaining cholesterol is from liver production.
Lipid metabolism is closely associated with the carbohydrate metabolism. The product of carbohydrate digestion is glucose, which converts into glycogen, and the excess is storing as fat for future energy needs.
Fat is an important energy source from food. More than 95% of dietary fat is long-chain triacylglycerols (TAG), the remaining being phospholipids (4.5%) and sterols. Every body cell in our body is capable of producing cholesterol by its own and thus only few cells require cholesterol supply.
Divide the lipid transport into the exogenous pathway, which refers to the dietary cholesterol absorbed through the intestine. In addition, the endogenous pathway refers to be liver produced (hepatic-derived) lipoproteins.
About 25% of the daily cholesterol requirement might be 300-500 mg comes from diet (exogenous). Balance 75% of the cholesterol might be 800-1,200 mg made by the body (endogenous). The liver synthesizes 20% of the total endogenous requirement and the balance by other body cells.
The exogenous (diet) and endogenous (synthesis) is a complex tightly regulated process referred as cholesterol homeostasis. This is a very complex, multifaceted with multiple layers of control. For example, when cholesterol intake is increased, the body will lower its cholesterol synthesis and/or their absorption (recycle) from the gut and vice versa. Re-absorption of the cholesterol is the dominant source of the cholesterol in the body; balance may be synthesis or absorb by the body.
Most of the dietary lipids are triglyceride; it has a glycerol backbone with three fatty acids each one attached to the carbon atom. Foodstuff contains phospholipids, sterols (cholesterol) and many minor lipids (including fat-soluble vitamins).
Two processes involved in the proper digestion and absorption of triglycerides, they are:
- Emulsification of lipid by Bile salt (from gallbladder) - Triglyceride form of lipids is insoluble in aqueous solution; bile salt emulsification makes the fat molecules to mix thoroughly with water in the diet.
- Hydrolysis of emulsified lipids by Lipase - Enzyme lipase digests the triglyceride’s molecules to derive mono-glyceride and fatty acids.
Small-intestinal mucosa absorbs free fatty acid and glycerol. These absorbed compounds are transports via the lymph system, assembled with dietary cholesterol and protein to form chylomicrons and released into blood streams.
Emulsification of lipid by Bile salt
Bile salt contains bile acid, cholesterol and phospholipids (lecithin). Bile acid is similar to a detergent molecule in structure. This structure helps the fat and disperses it into small packets known as emulsification (mixing of fat and water). Emulsification of fat is necessary, so that enzyme lipase can effectively break down fats.
Bile acids synthesized from cholesterol, which is vitally important for the digestion of fat. Bile acids reabsorbed in the metabolic recycling; however, still some are lost. To make up for this lost; the liver has to synthesize approximately 1,500 to 2,000 mg of cholesterol a day (equals seven to ten times the amount in a large egg).
Hydrolysis of emulsified lipids by Lipase
Lipase is a water-soluble enzyme present in the small intestine in a large quantity. It can act only on the surface of the triglyceride droplets. The smaller the droplet size, the greater the exposure area of lipids to lipase, which means more lipase activity, is possible. That is why, emulsification of fat is important prior to hydrolysis.
Pancreatic lipases are an enzyme, which carryout hydrolysis of triglyceride (most common in dietary fats) into mono-glyceride and free fatty acids. This hydrolyzed product in association with bile acids and other lipids form a complex structure called as micelles.
Fat absorption – exogenous pathway of cholesterol metabolism
The products of fat digestion are fatty acids and mono-glycerides. These products get into enterocyte (a type of cell present in the digestive tract which absorbs water and nutrients) by simple diffusion across the plasma membrane. Some fraction of fatty acids also gets into enterocyte via fatty acid transporter proteins in the membrane.
From enterocyte, the fatty acids and mono-glycerides are transporting into the smooth endoplasmic reticulum. Endoplasmic reticulum is an organelle (tiny structures with very specific functions found within a single cell that occurs in all cells). At endoplasmic reticulum, fatty acids and mono-glycerides are used to synthesis triglycerides. These triglycerides were packaging with cholesterol, lipoproteins and other lipids into particles called chylomicrons.
Chylomicrons are transport first into the lymphatic vessel by penetrates into each villus. Chylomicron rich lymph then drains into the lymphatic system, which rapidly flows into blood.
Another lipid of importance is cholesterol; absorbed in the small intestine. A specific protein carries cholesterol from the intestinal lumen into enterocyte. Here cholesterol is esterifies and incorporated into chylomicrons.
In the peripheral tissues (e.g. adipose), chylomicrons release their fat, when they meet tissues expressing lipoprotein lipase. It allows fats to be absorbed in the form of fatty acids & glycerol by breaking down of triglycerides. The chylomicrons now became smaller called chylomicron remnants. It produces empty HDL, as a bi-product of this process, which is then transport to the liver and removed.
Cholesterol in the bloodstream left unutilized are stored in the liver for future use.
The small intestine absorbs the dietary lipids and releases it into the blood stream as chylomicrons, neither VLDL nor LDL. However, digested carbohydrate foods are absorbed as glucose and released into the blood stream. Liver utilize this glucose, by converting it into VLDL and release it into the bloodstream.
Role of liver in fat metabolism
The cholesterol and lipids are absorbed through an exogenous pathway. After utilization, the excess quantity of fat reaches the liver. The liver can remove cholesterol from the body by converting it into bile salts and excrete it. Liver can also synthesis (endogenous) and release cholesterol in the blood circulation.
Digested fat is releases into the blood stream after a meal. Liver removes excess chylomicrons (triglyceride or fat packed with protein) from the blood circulation. Removed chylomicron is stored within the liver as lipid for future requirements. In between meals or during fasting, the liver manufactures fat from storage and releases cholesterol back into the blood circulation when needed. Even if there is no fat in dietary food, liver can produce the required quantity of fat from carbohydrates or protein foods. Even digested carbohydrate and protein foods are converted and stored as fat in the liver. This is, because fat can produce more energy compared to glucose of the same quantity.
Liver fat metabolism - Endogenous pathway of lipid metabolism
Liver removes excess chylomicrons (triglyceride or fat packed with protein) from the blood circulation. Removed chylomicron is stored within the liver as lipid for future requirements. In between meals or during fasting, the liver manufactures fat from storage and releases cholesterol back into the blood circulation when needed. Even if there is no fat in dietary food, liver can produce the required quantity of fat from carbohydrates or protein foods. Even digested carbohydrate and protein foods are converted and stored as fat in the liver. Why, because fat can produce more energy compared to glucose of the same quantity.
Role of bile salt in fat digestion
Bile salt has a detergent like molecule structure suited for interfacing lipid surfaces & water. It helps to disperse fat into small packets, and increases the exposing surface area to the enzyme lipase.
The liver uses cholesterol to synthesis bile salt, which contains bile acid, phospholipids, free fatty acids and cholesterol. The synthesized bile salt is stored in gallbladder and used when required. Bile secretion is stimulated by secretin (which stimulate liver), and CCK (which stimulate liver & gall bladder).
Adequate quantity of bile acid is necessary for proper fat metabolism. The bile salt in the digestive tract is absorbed and recycled at the end of the ileum. The liver produces about 0.6 g of fresh bile acid per day from cholesterol. This is adding up to the total bile acid pool of 3.0 g, which cycles 6 to 10 times per day. Approximately, 96% of the bile acid is re-absorbed in each cycle; the balance is lost with the stool.
Lipoprotein synthesis by the Liver
Liver synthesizes various lipoproteins (such as VLDL, LDL and HDL) involved in transportation of cholesterol and lipids throughout the body. The degree of lipid in a lipoprotein modifies its density, if lower the density more lipids it contains and vice versa. The five major types of lipoproteins are chylomicrons, very-low-density lipoprotein (VLDL), Intermediate-density lipoproteins (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
VLDL cholesterol synthesized in the liver; it delivers energy-rich triacylglycerol (TAG) to the cells throughout the body. VLDL strips out triacylglycerol (TAG) by the action of an enzyme lipoprotein lipase found on the endothelial cell surface. These enzymes further digest TAG to fatty acid and mono-glycerides, which oxidized for energy or re-synthesis to TAG.
The liver receives back the stripped and excess VLDL in the circulation using VLDL receptors. Liver remodeled it into LDL cholesterol. The main function of LDL is to transport cholesterol to cells through LDL receptor mediated endocytosis. Membranes consume LDL for energy or for the synthesis of steroidal hormones. LDL receptors present within the liver receives back the excess LDL in the circulation.
Liver and small intestine synthesis and secretes HDL precursor; it receives cholesterol from the circulation to form a mature HDL. This HDL along with cholesterol returns to the liver via various pathways.