Fat Metabolism

Dietary cholesterol represents only about one-third of our total cholesterol needs, remaining cholesterol is from liver production (endogenous sources).

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Lipid metabolism is closely associated with the carbohydrate metabolism; the product of carbohydrate digestion glucose is converting into glycogen, and the excess is converting into fats for storage.

Divide the lipid transport into the exogenous pathway, which refers to the dietary cholesterol absorbed through intestine, and the endogenous pathway, which refers to liver produced (hepatic-derived) lipoproteins.

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.

Fat digestion

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 that confirm for proper digestion and absorption of triglycerides, they are:

  • Emulsification of lipid by Bile salt - Triglycerides form of lipids are insoluble in aqueous solution, it must be physically broken down and suspended in it called emulsification.
  • Hydrolysis of emulsified lipids by Lipase - Enzyme is required to digest the triglyceride’s molecules to derive monoglyceride and fatty acids.

Emulsification of lipid by Bile salt

Bile salt contains bile acid, cholesterol and phospholipids (lecithin). Bile acid is similar to a detergent molecule structure. This structure of bile acid help emulsifies fat and disperses it into small packets known as emulsification (mixture of fat and water). Emulsification of fat is necessary, so that enzyme can effectively break down fats.

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 lipase is an enzyme, which carryout hydrolysis of triglyceride (most common in dietary fats) into monoglyceride 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 monoglycerides. 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 monoglycerides are transport 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 monoglycerides are used to synthesis triglycerides. These triglycerides are packaged with cholesterol, lipoproteins and other lipids into particles called chylomicrons.
Chylomicrons are transport first into the lymphatic vessel that penetrates into each villus. Chylomicron rich lymph then drains into the lymphatic system, which rapidly flows into blood.

Another lipid of importance that is absorbed in the small intestine is cholesterol. 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 breaks down of triglycerides. The chylomicrons are now smaller and called as chylomicron remnants. Empty HDL is produce as a bi-product of this process is then transport to the liver and removed.

Cholesterol in the bloodstream, if unutilized, then it is stored in the liver for future use.

Role of liver in fat metabolism

The cholesterol and lipids that are absorbed through an exogenous pathway after utilization, and the excess quantity reaches the liver. The liver is capable of remove cholesterol from the body by converting it to bile salts and excreting it. Liver can also synthesis 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.  Why, 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 function: Bile salt has a detergent like molecule structure suited for interfacing lipid surfaces & H2O. It helps to disperse fat into small packets, which helps to increase the exposing surface area to the enzyme lipase.

Bile salt synthesis & secretion: The liver from cholesterol synthesizes bile salt. Bile salt contains bile acid, phospholipids, free fatty acids and cholesterol. The synthesized bile salt in the liver is stored in gallbladder and used it when required. Bile secretion is stimulated by secretin (which stimulate liver), and CCK (which stimulate liver & gall bladder).

Bile recycling:  Adequate quantity of bile acid is necessary for proper fat metabolism. The bile salt in the digestive tract is absorbed at the end of the ileum, added to bile once again by the liver, and recycled. The liver produces about 0.6 g of new bile acid daily from cholesterol. This is adding into 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 in 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 four major types of lipoproteins are chylomicrons, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).

VLDL cholesterol is synthesized within the liver; its function is to deliver energy-rich triacylglycerol (TAG) to the cells throughout the body. VLDL strips down into triacylglycerol (TAG) by the action of an enzyme lipoprotein lipase found on the endothelial cells surface. These enzymes further digest TAG to fatty acid and monoglycerides, which oxidized for energy or re-synthesis to TAG.

VLDL receptors present within the liver receive back the excess VLDL in the circulation.

The stripped-down triacylglycerol from VLDL is remodeling in the liver 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 then returns to the liver via various pathways.

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