•Fig. 39.17 Leptinandhypothalamiccentersinvolvedinregulationofappetite.Seetextforexplanationsofabbreviations.
Intestinal enterocytes import both of these lipids and reesterify them to form TGs. TGs, along with fat-soluble vitamins, cholesterol, cholesterol esters, and phospholipids, are complexed with the protein ApoB48 to form chylomicrons. Chylomicrons are secreted, move into lymphatics, and then ultimately enter the circulation. While in the blood, other apoproteins such as ApoE and ApoC2 are transferred to the chylomicrons from HDL particles (one function of HDL is to provide a circulating reservoir of various apoproteins). This converts nascent chylomicrons into mature chylomicrons.
When chylomicrons enter the capillaries of adipose tissue during the digestive phase, they are partially digested by lipoprotein lipase (LPL). LPL is synthesized by adipocytes and secreted into the subendothelial space. LPL then binds to the endothelial membrane GPI-anchored protein GPIHBP1, which transports LPL to the luminal (apical) surface of the capillary endothelial cell. Once in this position, LPL molecules come into contact with chylomicrons. ApoC2 within chylomicrons is an activator of LPL dimerization and activity. FFAs are released from chylomicrons by LPL-mediated lipolysis of TG. (See earlier discussion and
Fig. 39.16B for an explanation of the processing of FFAs to stored TG within adipocytes.
LPL is also expressed in cardiac and skeletal muscle. Cardiac muscle preferentially uses FFA for energy and obtains most FFAs from lipoprotein particles (
Fig. 39.17 ). Thus cardiac muscle also extracts FFA from chylomicrons during the digestive phase. The activity of LPL in cardiomyocytes is highly regulated by local factors such as the local concentration of FFAs within the coronary capillary beds. LPL activity in skeletal muscle is relatively low during the digestive phase.
After lipolytic digestion within adipose tissue capillary beds, chylomicrons are converted to smaller, denser chylomicron remnants (CR) that now have reduced TG content. CR particles are able to penetrate the tunica intima of blood vessels at sites with endothelial dysfunction and thus are atherogenic. Because they still have ApoE protein associated with them, they can bind to one of several membrane receptors that recognize ApoE. CRs can also bind to specific glycolipids. Bound CRs are then endocytosed by hepatocytes (see
Fig. 39.17 ). Remaining FFAs that are released after endocytosis of CRs are reesterified into intrahepatic TG.
Fasting Phase: VLDL, IDL, and LDL
The source of circulating TG during the fasting phase is primarily the liver (see