This review addresses two major functions of apolipoprotein (apo) A5 including (1) its role
in maintaining normal plasma levels of circulating triglyceride (TG) and (2) its role as a component of
hepatic lipid droplets. ApoA5 is synthesized solely in the liver and circulating concentrations are extremely
low. In the plasma, ApoA5 associates with TG-rich lipoproteins and enhances TG hydrolysis
and remnant lipoprotein clearance. ApoA5 loss-of-function single nucleotide polymorphisms are associated
with reduced lipolysis, poor remnant clearance and concomitantly, hypertriglyceridemia. Although
there have been substantial breakthroughs in understanding pathophysiology associated with
secreted ApoA5, there is a paucity of knowledge on the functionality of intracellular ApoA5. However, recent studies indicate
that overexpression of intracellular ApoA5 is positively associated with accumulation of TG-rich lipid droplets in
hepatocytes. It is thought that ApoA5 may have a causal role in non-alcoholic fatty liver disease (NAFLD) and thus, may
serve as a target for developing therapeutics for NAFLD.
Keywords: Apolipoprotein A5, hepatocytes, hypertriglyceridemia, lipid-droplets, non-alcoholic fatty liver disease, single nucleotide
polymorphisms, triglyceride-rich lipoproteins.
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