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Fats and lipids are an essential component of the homeostatic function of the human body. Lipids contribute to some of the body’s most vital processes.
Lipids are fatty, waxy, or oily compounds that are soluble in organic solvents and insoluble in polar solvents such as water. Lipids include:
Fats and oils are esters made up of glycerol (a 3-carbon sugar alcohol/polyol) and 3 fatty acids. Fatty acids are hydrocarbon chains of differing lengths with various degrees of saturation that end with carboxylic acid groups. Additionally, fatty acid double bonds can either be cis or trans, creating many different types of fatty acids. Fatty acids in biological systems usually contain an even number of carbon atoms and are typically 14 carbons to 24 carbons long. Triglycerides store energy, provide insulation to cells, and aid in the absorption of fat-soluble vitamins. Fats are normally solid at room temperature, while oils are generally liquid.<1>
Lipids are an essential component of the cell membrane. The structure is typically made of a glycerol backbone, 2 fatty acid tails (hydrophobic), and a phosphate group (hydrophilic). As such, phospholipids are amphipathic. In the cell membrane, phospholipids are arranged in a bilayer manner, providing cell protection and serving as a barrier to certain molecules. The hydrophilic part faces outward and the hydrophobic part faces inward. This arrangement helps monitor which molecules can enter and exit the cell. For example, nonpolar molecules and small polar molecules, such as oxygen and water, can easily diffuse in and out of the cell. Large, polar molecules, for example, glucose, cannot pass freely so they need the help of transport proteins.
Another type of lipid is wax. Waxes are esters made of long-chain alcohol and a fatty acid. They provide protection, especially to plants in which wax covers the leaves of plants. In humans, cerumen, also known as earwax, helps protect the skin of the ear canal.
A further class includes steroids, which have a structure of 4 fused rings. One important type of steroid is cholesterol. Cholesterol is produced in the liver and is the forerunner to many other steroid hormones, such as estrogen, testosterone, and cortisol. It is also a part of cell membranes, inserting itself into the bilayer and influencing the membrane’s fluidity.<2>
The interaction between water-fearing and fat-loving displays more clearly during lipid transport in plasma. Both cholesterol and triglycerides are nonpolar lipid molecules. Therefore, they must travel in the polar plasma with the help of lipoprotein particles. The main goal of lipoprotein is to help transport lipids (hydrophobic) in water. The structure of lipoprotein consists of triglycerides, cholesterol, phospholipids, and apolipoproteins. Apolipoproteins mainly function as carrier proteins but also serve as cofactors for enzymes that metabolize lipoproteins and help in lipid component exchange among lipoproteins. Some examples of lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Each one is used in a different phase of lipid transport.<3>
Chylomicrons are large triglyceride-rich particle made in the endoplasmic reticulum of enterocytes of the small intestine. They play a role in carrying dietary triglycerides and cholesterol to peripheral tissues and the liver.<4> Apo B-48 is an apolipoprotein that is involved in chylomicron assembly, thus having a vital role in the absorption of dietary fats and fat-soluble vitamins.<5>
VLDLs are triglyceride-rich particles made in the liver.<4> Apo B-100 is important for VLDL production.<5>
IDL particles, which are cholesterol-rich, are created when triglycerides are removed from VLDL by muscle and adipose tissue.<4>
LDL particles are formed from VLDL and IDL particles and are also rich in cholesterol. LDL transports most of the cholesterol in the blood and is colloquially considered “bad cholesterol.”<4> Apo B-100 plays a key role by acting as a ligand for the LDL receptor-mediated uptake of LDL particles by the liver and other tissues.<5>
HDL particles are cholesterol and phospholipid-rich, and aid in reverse cholesterol transport from peripheral tissues to the liver, where it is removed. As such, HDL cholesterol is considered “good cholesterol”.<4>
To expand, the transport of plasma lipids involves two routes. One is an exogenous path for the transport of dietary triglycerides and cholesterol from the small intestine.<3> In the small intestine, triglycerides are broken down with the help of enzymes and bile acids, such as cholic acid. First, the early digestive products, such as free fatty acids, trigger release of the hormone Cholecystokinin (CCK) by the duodenum. CCK activity stimulates emptying of the gallbladder, which leads to bile release into the small intestine, and further triggers the pancreas to release pancreatic digestive enzymes into the intestine.<6> The detergent action of bile acids helps to emulsify fats, which allows easier hydrolysis by water-soluble digestive enzymes due to the increased surface area. One important enzyme, pancreatic lipase, breaks down triglycerides to produce free fatty acids and monoacylglycerol, which are absorbed by the intestinal mucosal cells with the help of mixed micelles that were created in the process.<7>
Fatty acids are made of 12 carbons or less and are absorbed through the intestinal mucosal villi. They enter the bloodstream through capillaries, reach the portal vein, and are taken to the liver with the help of lipid carrier proteins to be used for energy. However, longer-chain fatty acids are absorbed by the intestinal mucosa from the lumen, where they are re-esterified to form triglycerides and are incorporated into chylomicrons; the chylomicrons are then released into intestinal lymph, secreted into blood circulation through the thoracic duct, and attach to capillary walls in adipose and skeletal muscle tissue. At the attachment points, chylomicrons interact with the enzyme lipoprotein lipase, leading to triglyceride core breakdown and free fatty acid release. The fatty acids penetrate through the capillary endothelial cells and are either stored in adipose cells or oxidized in skeletal muscle cells. From the triglyceride core hydrolysis, remnants are removed from the plasma and brought to hepatic cells to be broken down by lysosomes. This causes the release of cholesterol, which can be turned into bile acids, integrated into VLDL, or even combined in bile.
The other pathway is via the endogenous system, in which cholesterol and triglycerides travel from the liver and other non-intestinal tissues into circulation. The liver produces triglycerides from carbohydrates and free fatty acids. These triglycerides are then released into plasma in the core of VLDL. The VLDL particles interact with lipoprotein lipase in tissue capillaries, causing triglyceride core hydrolysis and free fatty acid liberation. Some of the remnant particles are taken out of plasma and bind to hepatic cells. The rest of the remnant particles, however, transform into LDL particles, which then provide cholesterol to cells that have LDL receptors, such as the gonads, adrenal glands, skeletal muscle, lymphocytes, and kidneys.
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In addition to the functions mentioned above, when energy is needed, fat can also be broken down for energy. Glucagon (released during fasting) or epinephrine (released during exercise) activates adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase (MGL) for fatty acid liberation. These fatty acids can then be used for energy by most tissues with the help of mitochondria and the Krebs cycle.<3>