Triglyceride-rich lipoprotein clearance (TRL clearance)

Triglyceride-rich lipoprotein (TRL) clearance, often referred to as triglyceride-rich particle (TGRP) clearance, is a complex physiological process responsible for the removal of chylomicrons and very-low-density lipoproteins (VLDL) from the bloodstream (Hegele et al., 2014). This pathway is primarily driven by the enzymatic action of lipoprotein lipase (LPL), which hydrolyzes triglycerides into free fatty acids for use by peripheral tissues, followed by the rapid uptake of the resulting remnant particles by the liver (Hassing et al., 2012). Key molecular regulators of this process include Apolipoprotein C-III (ApoC-III) and Angiopoietin-like protein 3 (ANGPTL3), both of which act as inhibitors of clearance and are major targets for novel dyslipidemia therapies (Rosenson et al., 2020). Therapeutic enhancement of this process—via LPL activation or the neutralization of inhibitors—is critical for managing severe hypertriglyceridemia and reducing the risk of acute pancreatitis and atherosclerotic cardiovascular disease (Gaudet et al., 2015). Genetic or acquired defects in TRL clearance lead to the accumulation of atherogenic remnants and can result in extreme elevations of plasma triglycerides. Modern pharmacotherapy focusing on this clearance axis includes antisense oligonucleotides, monoclonal antibodies, and small molecules aimed at restoring or accelerating lipoprotein metabolic flux.

Other names

Triglyceride-rich particle clearanceRemnant lipoprotein clearanceChylomicron clearanceTGRP clearanceLipoprotein lipase activation pathway

Drugs targeting this physiological process enhance clearance by activating lipoprotein lipase (LPL) or by inhibiting endogenous inhibitors such as Apolipoprotein C-III and ANGPTL3, which promotes the enzymatic hydrolysis of triglycerides and the subsequent hepatic uptake of remnant particles via receptors like LRP1 and LDLR (Hegele et al., 2014; Gaudet et al., 2015).