Pathophysiology of hypertriglyceridemia

The importance of triglycerides as risk factor for CVD is currently under debate. The international guidelines do not include TG into their risk calculator despite the recent observations that plasma TG is an independent risk factor for CVD. The understanding of the pathophysiology of triglycerides opens up avenues for development of new drug targets. Hypertriglyceridemia occurs through 1. Abnormalities in hepatic VLDL production, and intestinal chylomicron synthesis 2. Dysfunctional LPL-mediated lipolysis or 3. Impaired remnant clearance. The current review will discuss new aspects in lipolysis by discussing the role of GPIHBP1 and the involvement of apolipoproteins and in the process of hepatic remnant clearance with a focus upon the role of heparin sulfate proteoglycans. Finally we will shortly discuss future perspectives for novel therapies aiming at improving triglyceride homeostasis. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

► Peripheral lipolysis is dependent upon GPIHBP1 and LPL.
► The role of HSPG is limited.
► The role of apoAV in peripheral lipolysis remains to be elucidated.
► Hepatic remnant clearance involves receptor-mediated uptake through LDLr, LRP1 or HSPG.
► Modulating factors resulting in hepatic loss of function of HSPG lead to impaired hepatic TG clearance.