hepatic lipase

**Function / Location** - Synthesized by hepatocytes. Anchored by heparan sulfate proteoglycans to the endothelial surface of hepatic sinusoids. It is not freely circulating, but it can be released by heparin. - Hydrolyzes triglycerides (TG) and phospholipids in IDL, HDL (especially HDL2), and chylomicron remnants. - Actions: 1. IDL → LDL: removes TG from IDL, leaving a cholesterol-rich LDL particle. 2. HDL2 → HDL3: removes TG and phospholipids from HDL2, producing smaller, denser, lipid-poor HDL3. This lipid-poor HDL is better able to accept cholesterol from tissues (via ABCA1) and cycle through reverse cholesterol transport. 3. Ligand function: acts as a bridging ligand that promotes hepatic uptake of remnant lipoproteins and HDL cholesteryl ester (via SR-B1), independent of its catalytic activity. - Does not require apoC-II. This distinguishes it from lipoprotein lipase (LPL).

**Comparison with other lipases (high-yield)** - Lipoprotein lipase (LPL): on capillary endothelium of adipose tissue, muscle, and heart. Activated by apoC-II. Cleaves TG in chylomicrons and VLDL. Induced by insulin. - Hepatic lipase: on hepatic sinusoids. Works on IDL and HDL. Not dependent on apoC-II. - Endothelial lipase: mainly phospholipase activity on HDL. - Hormone-sensitive lipase: intracellular in adipocytes. Mobilizes stored TG. Activated by epinephrine and glucagon, inhibited by insulin. - Pancreatic lipase: dietary TG digestion in the intestinal lumen. Inhibited by orlistat. - LCAT: esterifies cholesterol on HDL (activated by apoA-I).

**Regulation** - Activity is increased by androgens, which lowers HDL in men. Activity is decreased by estrogen, which raises HDL in premenopausal women. - Increased in insulin resistance, visceral obesity, and type 2 diabetes. This yields small dense LDL and low HDL. - Fibrates and statins have modest effects. Thiazolidinediones may reduce activity.

**Hepatic lipase deficiency (rare, autosomal recessive; LIPC gene, chromosome 15)** - Elevated TG and cholesterol from accumulation of IDL, VLDL remnants, and TG-rich HDL and LDL particles. Often shows a β-VLDL pattern. - Large, buoyant, TG-enriched HDL (HDL2) with variable HDL-C levels. - Increased risk of premature atherosclerosis and coronary artery disease. - Xanthomas are possible. Pancreatitis is less common than with LPL or apoC-II deficiency. - Differential: familial dysbetalipoproteinemia (type III), which is due to apoE2/E2 and shows palmar xanthomas and broad β band. Also LPL or apoC-II deficiency (type I), which causes chylomicronemia, eruptive xanthomas, lipemia retinalis, and pancreatitis.

**Exam pearls** - "Hepatic lipase = IDL → LDL." Also remember "HDL2 → HDL3." - The Fredrickson classification does not have a specific HL deficiency type. It is usually seen as a mixed hyperlipidemia. - Postheparin plasma assays show decreased HL activity in deficiency. - Don't confuse HL (liver, IDL/HDL) with LPL (peripheral capillaries, chylomicrons/VLDL, apoC-II).