Content Reviewers:Viviana Popa, MD
With Hypertriglyceridemia, hyper means high, -emia refers to blood levels, and triglycerides are the most abundant fatty molecules in an organism.
So, hypertriglyceridemia is when there’s excess triglycerides in the blood.
Specifically, hypertriglyceridemia is when there are more than 150 mg of triglycerides per deciliter of blood.
Triglycerides can be deposited in subcutaneous tissue and around organs and function as energy storage in the body.
We can either get triglycerides from our diet, which are called exogenous triglycerides; or our liver can synthesize them from other molecules, in which case they’re called endogenous triglycerides.
Now, exogenous triglycerides are first absorbed in the small intestine, and then they undergo a series of changes in order to be transported and deposited in the body.
So, after triglycerides are absorbed, they enter the intestinal mucosal cells, inside of which they’re coupled with various apolipoproteins and phospholipids to create chylomicrons, which are one type of lipoprotein.
Lipoproteins are made up of lipids (like triglycerides or cholesterol) or phospholipids and proteins (like apolipoproteins CII, CIII, or E).
The main job of lipoproteins is to carry insoluble molecules, like triglycerides, from the intestines to the circulation.
That's because, normally, triglycerides are insoluble in liquid environments like blood.
Now, the newly created chylomicrons enter the bloodstream and bind to the wall of capillaries in adipose and skeletal muscle tissue.
At the binding site, they interact with the lipoprotein lipase enzyme leading to the breakdown of the triglyceride core and liberation of free fatty acids directly into the adipocytes or skeletal muscle cell, where they’re either stored or used for energy.
After triglycerides leave the chylomicron, what’s left is called a remnant chylomicron.
Remnant chylomicrons are high in cholesterol esters and they’re cleared from circulation by the liver when the apolipoprotein E binds to Apo-B100/E receptor on the hepatic cell membrane.
The remnant chylomicrons are then degraded by acid hydrolases to a mixture of amino acids, free fatty acids, and cholesterol.
Now let’s switch gears and look at how endogenous triglycerides are synthesized.
First, the liver makes another type of lipoproteins called very low-density lipoproteins, or VLDL.
The fatty acids are either synthesized from scratch from carbohydrates or released from adipose tissue.
Then, the liver exports the triglyceride-rich VLDL molecules into the bloodstream, which carries them to muscle and adipose cells.
Here, VLDL are cleaved by lipoprotein lipase to intermediate-density lipoproteins(IDL), also called VLDL remnants.
The IDL are further metabolized to low-density lipoproteins, LDL, and are released into the bloodstream, which are taken up by the LDL receptor in numerous tissues including the liver.
Ok, so hypertriglyceridemia can result from anomalies in either the exogenous or the endogenous pathways, but in either case, excessive triglyceride levels accumulate in the body.
Now, atherosclerosis can occur via a pathway that involves an endothelial dysfunction.
This dysfunction allows small triglycerides remnants to reach the intimal layer where they get taken up by the macrophages, leading to the formation of foam cells.
Foam cells promote fatty streak formation: the precursor of atherosclerotic plaque.
Secondary causes are more common, and they may be associated with obesity, diabetes mellitus, high carbohydrate diets, hypothyroidism, or increased alcohol intake, all of which impact lipid metabolism.
With obesity-associated hypertriglyceridemia, there is a hepatic overproduction of VLDL and decreased circulating triglycerides breakdown.
Finally, high-carbohydrate diets, where carbohydrates make up more than 60% of the total caloric intake, lead to increased carbohydrate breakdown and increased production of free fatty acids as a consequence.
The excess free fatty acids can be used to synthesize more triglycerides, therefore causing hypertriglyceridemia