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Lipoprotein lipase (LPL) is an extracellular enzyme on the vascular endothelial surface that degrades circulating triglycerides in the bloodstream. These triglycerides are embedded in very low-density lipoproteins (VLDL) and chylomicrons traveling through the bloodstream. The role of lipoprotein lipase is significant in understanding the pathophysiology of type one familial dyslipidemias, or hyperchylomicronemia, and its clinical manifestations. LPL also plays an essential role in understanding the cardiac pharmacology of fibrates as a class of medications and in managing patients with high levels of serum triglycerides. This review will explore lipoprotein lipase's function, pathophysiology, and clinical relevance.[1]

The pathophysiology of lipoprotein lipase is evident in familial dyslipidemias (specifically type one) or hyperchylomicronemia. Hyperchylomicronemia is an autosomal recessive genetically inherited disease in which there is a significant increase in levels of triglycerides, >1000, such that the plasma of these patients has a milky appearance. There are also significantly increased chylomicron levels in these individuals' blood.[5] In both type one familial dyslipidemia or hyperchylomicronemia, there is severe LPL dysfunction; this is because of LPL deficiency and LPL co-factor deficiency, or apolipoprotein C2 deficiency, which is necessary for activation of lipoprotein lipase. LPL typically removes triglycerides from chylomicrons; if this process does not function, initial triglyceride breakdown cannot occur. Therefore, triglycerides will build up in the serum, and chylomicrons will grow very large as they are full of triglycerides, which are not undergoing removal.[6] Patients with hyperchylomicronemia present with recurrent pancreatitis, enlarged liver, and xanthomas because of a lack of triglyceride removal from chylomicrons and increased serum triglycerides and chylomicrons levels. This buildup eventually leads to triglyceride accumulation in the pancreas, in the liver, and deposits on the skin, causing these clinical manifestations. Xanthomas occur because of plaques of lipid-laden histiocytes, as macrophages in the bloodstream endocytose excess serum triglycerides. Clinically, xanthomas appear as skin bumps or along the eyelids of patients with high serum lipid levels.[7] Elevated triglycerides can cause acute pancreatitis, which may involve increased plasma chylomicrons. These chylomicrons can obstruct capillaries, and this may cause decreased blood flow and, ultimately, ischemia. When vessel damage occurs, this can cause pancreatic lipases to have access to serum triglycerides. Pancreatic lipases may break down these triglycerides, releasing triglyceride breakdown products, including free fatty acids. This increase in free fatty acids can injure the tissue of the pancreas leading to pancreatitis.[7]

Elevated triglycerides can cause acute pancreatitis, which may involve increased plasma chylomicrons. These chylomicrons can obstruct capillaries, and this may cause decreased blood flow and, ultimately, ischemia. When vessel damage occurs, this can cause pancreatic lipases to have access to serum triglycerides. Pancreatic lipases may break down these triglycerides, releasing triglyceride breakdown products, including free fatty acids. This increase in free fatty acids can injure the tissue of the pancreas leading to pancreatitis.[7] Treatment for type 1 familial dyslipidemia or hyperchylomicronemia is a very low-fat diet. With careful monitoring of diet, patients often have normal lifespans. Additionally, with tight dietary lipid control, patients have no apparent increased risk for atherosclerosis. Orlistat is a medication that can also improve hyperchylomicronemia by decreasing the risk of pancreatitis; it is a pancreatic lipase inhibitor given before meals.[8]