Triglycerides Triglycerides in serum are incorporated into lipoproteins. Lipoproteins are composed of a coat of phospholipid, cholesterol and proteins (apolipoproteins) enclosing a hydrophobic center of cholesterol esters and triglycerides. There are four classes of lipoproteins, high-density lipoproteins (HDL), low-density lipoproteins (LDL), very low-density lipoproteins (VLDL) and chylomicrons (CM). All these lipoprotein classes contain triglycerides, however the highest triglyceride concentrations are found in CM and VLDL. Lipoprotein classes Chylomicrons CM contain 90% triglyceride, 3% cholesterol and apolipoprotein B, C and E. They carry lipid from the gastrointestinal system to adipose tissue and skeletal muscle. Lipoprotein lipase, an enzyme located in the vascular endothelium, hydrolyzes CM yielding fatty acids and glycerol and cholesterol-rich CM remnants. Fatty acids and glycerol are taken up by adipose tissue and skeletal muscle and re-converted into triglycerides for long-term fat storage. CM-remnants are taken up by the liver through remnant (apolipoprotein E) receptors. Very low-density lipoproteins VLDL contain 62% triglycerides, 12% cholesterol, and apolipoprotein B100, E and C. They are produced in the liver from free fatty acids. They are the main carrier of triglycerides in the fasting state, transporting triglycerides and cholesterol from the liver to peripheral tissues (via lipoprotein lipase hydrolysis). After hydrolysis, a VLDL cholesterol-rich remnant remains. This can be taken up by remnant receptors in the liver or converted to LDL by hepatic lipase. Low-density lipoproteins These contain approximately 8% triglyceride, 42% cholesterol and apoliprotein B100. LDL are responsible for delivering cholesterol to peripheral tissues, including the adrenal glands, ovary and testes, through LDL receptors. High-density lipoproteins These contain 1-2% triglcyeride, 30-36% cholesterol and apolipoprotein A, E and C. They are produced in the gastrointestinal system and the liver. They bind unesterified cholesterol released from tissues (with the help of the enzyme lecithin acylcholesterol transferase - LCAT). They are taken up by remnant receptors in the liver and are thus involved in reverse cholesterol transport (delivering cholesterol from peripheral tissues to the liver). Hormones involved in fat metabolism Lipoprotein lipase (LPL) Lipoprotein lipase is found in vascular endothelium. It is activated by insulin, ACTH, TSH, glucagon and thyroid hormone. Its activity is enhanced by heparin. As discussed above, lipoprotein lipase hydrolyzes CM and VLDL to free fatty acids and glycerol and VLDL-remnants, respectively. Apolipoprotein C is essential for activation of LPL. Hepatic lipase This enzyme hydrolyzes surface phospholipids on lipoproteins and is responsible for converting VLDL to LDL. Hormone sensitive lipase This enzyme is responsible for lipolysis (mobilization of triglycerides from adipose tissue to yield free fatty acids and glycerol). The enzyme is stimulated by catecholamines, growth hormone, thyroxine, corticosteroids and prostaglandins. It is inhibited by insulin. Fatty acids are transported to the liver (free or albumin-bound), where they are taken up and used for energy (beta oxidation), combined with triglycerides to form VLDL or incorporated into ketones. Therefore, lipolysis will increase VLDL production. Hyperlipemia Hyperlipemia is due to an increase in plasma lipids, namely cholesterol and triglycerides. Hypertriglyceridemia produces visible lipemia and indicates an elevation in CM or VLDL. When hyperlipemia is from increased CM, e.g. postprandial hyperlipemia, CM will form a fat layer above a clear infranatant when serum or plasma samples are refrigerated. When hyperlipemia is due to increased VLDL, a fat layer does not form, and the sample is turbid (lipemic). When there is a combination of both CM and VLDL, a fat layer will form above a turbid infranatant. This is shown in the image below. Hypercholesterolemia is generally caused by an increase in LDL and HDL and does not produce a visible hyperlipemia. It is important to remember that lipemia will interfere with laboratory tests, especially hematologic and biochemical tests. Therefore, fasting samples should always be collected for testing. For more information on the effect of lipemia on these tests, refer to analytical variables. [Hypertriglyceridemia]

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