Triglycerides (within chylomicrons and very low-density lipoproteins) (TG (within CM and VLDL))

Triglycerides within chylomicrons and very low-density lipoproteins (VLDL) are the primary vehicles for transporting fatty acids through the aqueous environment of the bloodstream (StatPearls: https://www.ncbi.nlm.nih.gov/books/NBK545173/). Chylomicrons are formed in the intestines to transport dietary lipids, while VLDL is synthesized in the liver to distribute endogenous lipids to peripheral tissues (Nature Reviews Cardiology: https://www.nature.com/articles/s41569-019-0211-4). These triglyceride-rich lipoproteins (TRLs) are essential for energy homeostasis, providing fuel for muscular activity and substrates for adipose tissue storage (Circulation Research: https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.114.303061). Pathologically high levels of these particles, a condition known as hypertriglyceridemia, are associated with an increased risk of atherosclerotic cardiovascular disease and, at extreme levels, acute pancreatitis (NIH: https://www.nhlbi.nih.gov/health/high-blood-triglycerides). Although triglycerides are metabolic substrates rather than traditional drug targets like receptors or enzymes, they serve as critical biomarkers and the ultimate therapeutic objective for various lipid-lowering agents. Drugs such as fibrates and omega-3 fatty acids lower these levels by enhancing the activity of lipoprotein lipase or reducing hepatic secretion (PubMed: https://pubmed.ncbi.nlm.nih.gov/21508345/). Newer antisense and monoclonal antibody therapies target regulatory proteins like APOC3 and ANGPTL3 to accelerate the clearance of these lipoproteins from the circulation (NEJM: https://www.nejm.org/doi/full/10.1056/NEJMoa2400236).

Other names

TriacylglycerolsTriglyceride-rich lipoproteinsTRLsVLDL-TGChylomicron-TG

Therapeutic reduction of these lipoproteins is achieved through the activation of lipoprotein lipase (LPL), inhibition of hepatic VLDL synthesis, or the antagonism of regulatory proteins such as Apolipoprotein C-III (APOC3) and Angiopoietin-like protein 3 (ANGPTL3).