Lipids Metabolism Disorders: Pathophysiology 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 of the body from the entry of water-soluble substances on the skin
  • Prevention of 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

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.

Lipoprotein Functions and Apoprotein Mechanisms

LipoproteinFunctionApoproteinMechanism
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

Quick Reference: Lipids Metabolism Disorders

Primary Lipid Metabolism DisorderMajor Signs and SymptomsKey Laboratory TestsConventional TherapiesNaturopathic Therapies
Familial HypercholesterolemiaTendon xanthomasVery high cholesterol: 800-1200 mg/dlHMG Co A reductase inhibitors, bile acid resins, Gemfibrozil, niacinHigh fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines
Familial HypertriglyceridemiaNon specific symptomsVery high triglycerides, normal cholesterolGemfibrozil, HMG Co A reductase inhibitors, niacinHigh fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines
Polygenic HypercholesterolemiaNon specific symptomsHigh cholesterolHMG Co A reductase inhibitors, bile acid resins, Gemfibrozil, niacinHigh fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines
Familial DysbetalipoproteinemiaPlanar xanthomas on palms and soles of feetHigh cholesterol, high triglycerides, abnormal apoprotein E phenotypeGemfibrozil, HMG Co A reductase inhibitors, niacinHigh fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines
Familial Combined HyperlipidemiaNon specific symptomsHigh cholesterol, high triglycerides, high Apoprotein BHMG Co A reductase inhibitors, bile acid resins, Gemfibrozil, niacinHigh fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines
Secondary Lipid Metabolism Disorder
Diabetes MellitusNon specific symptomsVery high cholesterolHMG Co A reductase inhibitors, bile acid resins, Gemfibrozil, niacinHigh fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines
HypothyroidismFatigue, Low body temperatureVery high cholesterolHMG Co A reductase inhibitors, bile acid resins, Gemfibrozil, niacin, SynthroidHigh fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines, Armour, T3, T4
Wilson’s SyndromeFatigue, Low body temperatureHigh cholesterolHMG Co A reductase inhibitors, bile acid resins, Gemfibrozil, niacinHigh fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines, T3 therapy
Nephrotic SyndromeEdemaHigh cholesterol, high triglyceridesHMG Co A reductase inhibitors, bile acid resins, Gemfibrozil, niacin, steroidsSalt restriction, high fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines
Obstructive Liver DiseaseJaundiceHigh cholesterol, high triglyceridesSurgerySalt restriction, high fiber diet, decreased saturated fats, increased omega oils, niacin, red yeast, botanical medicines, milk thistle

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 CII. Lipoprotein lipase breaks down Apo E and Apo CII, 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, 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 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.