Physiology Review
Endocrine function and lipid metabolism are interwoven in innumerable ways and more connections are being discovered on a regular basis. For example, human growth hormone (hGH) lowers total cholesterol, while increased cortisol levels have the opposite effect. Menopause is known to decrease HDL, while LDL levels rise. Hyperlipidemia is a standard screening test for thyroid dysfunction. Recently, Gerald Reaven at Stanford University discovered that hyperinsulinemia (Metabolic Syndrome X) raises triglycerides and LDL levels, thereby increasing cardiovascular risk. Clearly consideration of endocrine function is important in assessing any dyslipedemia.
Functions of Lipids
Lipids are fat-soluble substances that have many essential roles in the body. They are integral constituents of all cell membranes in the body.
- Protection the body from the entry of water-soluble substances on the skin
- Prevention evaporation of water from the body
- Nerve conduction
- Neurotransmitter production
- Digestion of dietary fats
- Transportation and storage of energy rich compounds
- Molecular basis of the steroid hormone molecules
Five Kinds of Lipids
Cholesterol
Cholesterol ester Phospholipid
Triglyceride
Unesterified fatty acid
Lipoproteins
Lipoproteins transport water insoluble lipids from one site of the body to the other. Lipoproteins surround lipids with a coating of water-soluble proteins and phospholipids. Apoproteins are located on the surface of lipoproteins, which function as molecular structures that can bind to receptors in peripheral tissues.
Four Major Lipoproteins
Chylomicrons
Very Low Density Lipoproteins (VLDL)
Low Density Lipoproteins (LDL)
High Density Lipoproteins (HDL)
Lipoprotein Functions and Apoprotein Mechanisms
| Lipoprotein | Function | Apoprotein | Mechanism |
| Chylomicrons | Transport dietary cholesterol from the small intestine to muscles and fat tissue | Apoprotein C-II | Used as a cofactor for lipoprotein lipase, which removes triglycerides from chylomicrons and VLDL |
| VLDL | Transports triglycerides produced from the liver to fat and muscle tissue | Apoprotein C-II | Used as a cofactor for lipoprotein lipase, which removes triglycerides from chylomicrons and VLDL |
| LDL | Transports liver produced cholesterol to the rest of the body | Apoprotein B | Binds to peripheral and hepatic receptors for LDL |
| HDL | Transports cholesterol from peripheral tissue back to the liver | Apoprotein A | Binds to peripheral receptors for HDL |
VLDL and LDL Metabolism
The liver produces very low-density lipoproteins (VLDL) in order to have cholesterol transported in a manner that can move through the blood. Very low-density lipoproteins contain cholesterol and triglycerides in the middle, encoated with three apolipoprotein structures that are surface molecules to be recognized by lipoprotein lipase. The apolipoproteins consist of Apo E, Apo B 100, and Apo C2. Lipoprotein lipase breaks down Apo e and Apo C11, leaving Apo B 100.
With the aid of lipoprotein lipase found in the endothelial walls of vessels, VLDL is then converted into LDL, where the cholesterol can be either used as substrates for steroid synthesis or for bile acids. The rest is deposited in extra hepatic tissue or oxidized in the arterial walls, becoming the precursor of plaque formation.
In general in our society of excess, we must try to decrease the oxidation of LDL and help with the elimination via bile acid secretion. Most people’s LDL is high due to genetic, lifestyle, and other inheritance factors. It is often due to a secondary cause, such as hypothyroidism and insulin resistance.
LDL receptors are made in the endoplasmic reticulum and further processed in the golgi apparatus where they are excreted. The cholesterol synthesized with HMG CoA reductase enzyme is then either stored with the aid of the enzyme cholesterol acyltranferase, or then exported into the plasma for the formation of cell membranes, steroid synthesis, or bile acids.
HDL Metabolism
The liver has a central role in cholesterol balance. The liver is the main organ in both the production of cholesterol and the breaking down of cholesterol. HDL (high density lipoprotein) particles are produced in the liver and released into the blood. The function of HDL particles is to carry excess cholesterol from the cells back to the liver. The cholesterol returned to the liver can be reused or excreted in the bile.
Since HDL particles take cholesterol from the cells and remove it, it has earned the name “good” cholesterol. Higher levels of HDL in the blood are associated with less risk of cardiovascular disease. HDL levels are increased by exercise and decreased by excess insulin release. Just as there are genetic conditions in which people overproduce LDL, there are also some people who have a disposition to produce high levels of HDL. These people have very low rates of heart disease even into old age, and this seems to be unaffected by dietary fat intake.
