VLDL Metabolism (Endogenous Triglyceride Metabolism)

VLDL assembly and secretion is similar to the corresponding pathway for chylomicrons. Triglycerides and cholesterol esters are packaged into the core of the lipoprotein particle. However, in contrast to intestinal chylomicron secretion, hepatocytes secrete VLDL directly into the bloodstream. In the bloodstream, VLDL is acted upon by lipoprotein lipase, delivering its triglyceride cargo to muscle and adipose tissue. The resulting VLDL remnant particle, also termed IDL (intermediate density lipoprotein), is further metabolized as discussed below.

In both the liver and the intestine, triglyceride incorporation into lipoprotein particles requires the action of microsomal triglyceride transfer protein (MTP). MTP resides in the lumen of the endoplasmic reticulum (ER) and facilitates the transfer of triglycerides and cholesterol ester from the cytoplasmic side of the ER to the interior of the lipoprotein particle. Mutations in MTP cause abetalipoproteinemia, an inability to secrete chylomicrons and VLDL.

Figure 5 Sources of fatty acid for hepatic triglyceride synthesis. (1) Adipose tissue lipolysis, catalyzed by hormone- sensitive lipase, provides fatty acids that travel through the bloodstream to the liver. (2) Chylomicron remnants still carry some triglyceride and are cleared from the circulation by the liver. (3) Carbohydrate is converted to fatty acids when glycogen stores are maintained.

In humans, the liver is a major lipogenic tissue. The liver is able to transform excess carbohydrate or protein into fat (remember, when we eat too much of anything we get fat!). Fatty acid substrates for hepatic triglyceride production are derived from three sources (Fig. 5): (1) a continuous supply of albumin-bound fatty acid to the liver, primarily from adipose tissue triglyceride stores (after a meal this source drops, due to the antilipolytic action of insulin), (2) dietary fat already transported in chylomicrons delivered to the liver, and (3) carbohydrate in excess of the liver’s capacity for storage as glycogen.