APOC-III: a Gatekeeper in Controlling Triglyceride Metabolism

Abstract

Purpose of review: Apolipoprotein C-III (ApoC-III) is a widely known player in triglyceride metabolism, and it has been recently recognized as a polyhedric factor which may regulate several pathways beyond lipid metabolism by influencing cardiovascular, metabolic, and neurological disease risk. This review summarizes the different functions of ApoC-III and underlines the recent findings related to its multifaceted pathophysiological role.

Recent findings: The role of ApoC-III has been implicated in HDL metabolism and in the development of atherosclerosis, inflammation, and ER stress in endothelial cells. ApoC-III has been recently considered an important player in insulin resistance mechanisms, lipodystrophy, diabetic dyslipidemia, and postprandial hypertriglyceridemia (PPT). The emerging evidence of the involvement of ApoC-III in the in the pathogenesis of Alzheimer's disease open the way to further study if modification of ApoC-III level slows disease progression. Furthermore, ApoC-III is clearly linked to cardiovascular disease (CVD) risk, and progression of coronary artery disease (CAD) as well as the calcification of aortic valve and recent clinical trials has pointed out the inhibition of ApoC-III as a promising approach to manage hypertriglyceridemia and prevent CVD. Several evidences highlight the role of ApoC-III not only in triglyceride metabolism but also in several cardio-metabolic pathways. Results from recent clinical trials underline that the inhibition of ApoC-III is a promising therapeutical strategy for the management of severe hypertriglyceridemia and in CVD prevention.

Keywords: ApoC-III; Cardiovascular disease burden; Post prandial lipemia; Therapeutic target; Triglyceride-rich lipoproteins (TRLs).

Fig. 1

Schematic representation of ApoC-III roles and functions discussed in this review. ApoC-III prevents TRL clearance via both low-density lipoprotein receptors (LDLRs) and LDLR-related protein; bidirectional transfer between VLDL and HDL in a CETP-independent manner; it inhibits LPL and obstructs the hepatic uptake of TG-rich lipoproteins, enhances proinflammatory signaling pathways (IL-6/BMP-2), promotes the expression of VCAM-1 and MCP-1 and expression of oxidative stress and ER stress-related proteins, and correlates to diabetes mellitus and insulin-resistance; obesity amplifies insulin resistance through endothelial cells; it is involved in the development of hypertriglyceridemia observed in lipodystrophy, increases tumor necrosis factor-α (TNF-α) levels, and may promote the efflux of Amyloid β from the brain