Lipoprotein lipase expression is regulated by the nutritional state and hormonal level, and it is synthesized by adipose tissue, as well as cardiac and skeletal muscle. When insulin levels are elevated in the fed state, adipose tissue increases the synthesis of LPL, while muscle tissue decreases its synthesis. Conversely, fasting leads to decreased insulin levels, which favors LPL synthesis in muscle. The highest concentration of LPL is found in cardiac muscle, reflecting its use of fatty acids (FA) as a significant energy source for cardiac function.

During the circulation of chylomicrons, more than 90% of the triglycerides (TAG) in its core are degraded by LPL. This degradation causes the chylomicron to decrease in size and increase in density. The C apolipoproteins are returned to high-density lipoprotein (HDL), while apolipoproteins B and E are not. The remaining particle, known as a remnant, is quickly removed from the circulation by the liver. The liver contains lipoprotein receptors that recognize apo E, and these receptors allow chylomicron remnants to bind and be taken into the hepatocytes via endocytosis. Inside the hepatocytes, the endocytosed vesicle fuses with a lysosome, resulting in the hydrolytic degradation of the apolipoproteins, cholesteryl esters, and other components of the remnant. This degradation releases amino acids, free cholesterol, and fatty acids. The receptor is then recycled. 

Very-low-density lipoprotein (VLDL) metabolism involves the production of VLDL in the liver. VLDL is mainly composed of endogenous triglycerides (TAG) and its primary function is to transport this lipid from the liver to peripheral tissues. LPL degrades the TAG in VLDL in a similar manner to chylomicrons. Nonalcoholic fatty liver, also known as hepatic steatosis, occurs when there is an imbalance between hepatic TAG synthesis and the secretion of VLDL. This condition can be seen in obesity and type 2 diabetes mellitus.

VLDL is secreted directly into the bloodstream by the liver as nascent particles containing apo B-100. To become fully functional, VLDL requires apo CII and apo E from circulating HDL. Similar to chylomicrons, apo C-II is necessary for LPL activation. Abetalipoproteinemia is a rare hypolipoproteinemia caused by a defect in microsomal triglyceride transfer protein (MTP), resulting in the inability to load apo B with lipid. Consequently, fewer VLDL or chylomicrons are formed, and TAG accumulates in the liver and intestine. Fat-soluble vitamin absorption is also decreased, and low-density lipoprotein (LDL) levels are low.

As VLDL circulates, LPL degrades TAG, causing VLDL to decrease in size and become denser. The surface components, including the C and E apolipoproteins, are returned to HDL, while apo B-100 remains on the particles. Additionally, an exchange reaction occurs between VLDL and HDL, where some TAG from VLDL is transferred to HDL, and concomitantly, cholesteryl esters are transferred from HDL to VLDL. Cholesteryl ester transfer protein (CETP) facilitates this exchange reaction, as depicted in Figure 18.18.
Lipoprotein lipase expression: LPL is synthesized by adipose tissue and by cardiac and skeletal muscle. Expression of the tissue-specific isozymes is regulated by nutritional state and hormonal level. For example, in the fed state (elevated insulin levels), LPL synthesis is increased in adipose but decreased in muscle tissue. Fasting (decreased insulin) favors LPL synthesis in muscle. [Note: The highest concentration of LPL is in cardiac muscle, reflecting the use of FA to provide much of the energy needed for cardiac function.] 6.
Chylomicron remnant formation: As the chylomicron circulates, and >90% of the TAG in its core is degraded by LPL, the particle decreases in size and increases in density. In addition, the C apolipoproteins (but not apo B or E) are returned to HDL. The remaining particle, called a remnant, is rapidly removed from the circulation by the liver, whose cell membranes contain lipoprotein receptors that recognize apo E (see Fig. 18.16). Chylomicron remnants bind to these receptors and are taken into the hepatocytes by endocytosis. The endocytosed vesicle then fuses with a lysosome, and the apolipoproteins, cholesteryl esters, and other components of the remnant are hydrolytically degraded, releasing amino acids, free cholesterol, and FA. The receptor is recycled. [Note: The mechanism of receptor-mediated endocytosis is illustrated for LDL in Fig. 18.20.]
C. Very-low-density lipoprotein metabolism
VLDL are produced in the liver (Fig. 18.17). They are composed predominantly of endogenous TAG (~60%), and their function is to carry this lipid from the liver (site of synthesis) to the peripheral tissues. There, the TAG is degraded by LPL, as discussed for chylomicrons (see p. 228). [Note: Nonalcoholic fatty liver (hepatic steatosis) occurs in conditions in which there is an imbalance between hepatic TAG synthesis and the secretion of VLDL. Such conditions include obesity and type 2 diabetes mellitus (see p. 343).] 1.
Release from the liver: VLDL are secreted directly into the blood by the liver as nascent particles containing apo B-100. They must obtain apo CII and apo E from circulating HDL (see Fig. 18.17). As with chylomicrons, apo C-II is required for activation of LPL. [Note: Abetalipoproteinemia is a rare hypolipoproteinemia caused by a defect in MTP, leading to an inability to load apo B with lipid. Consequently, few VLDL or chylomicrons are formed, and TAG accumulates in the liver and intestine. Absorption of fat-soluble vitamins is decreased. LDL are low.] 2.
Modification in the circulation: As VLDL pass through the circulation, TAG is degraded by LPL, causing the VLDL to decrease in size and become denser. Surface components, including the C and E apolipoproteins, are returned to HDL, but the particles retain apo B-100. Additionally, some TAG are transferred from VLDL to HDL in an exchange reaction that concomitantly transfers cholesteryl esters from HDL to VLDL. This exchange is accomplished by cholesteryl ester transfer protein (CETP), as shown in Figure 18.18.