Metabolic characterisation of a rare genetic variation within APOC3 and its lipoprotein lipase independent effects

Apolipoprotein C3 is a potential new target for reducing blood triglyceride levels and cardiovascular risk. 

This paper characterizes the effects of the rare APOC3 loss of function mutation on lipid metabolism in two large European population cohorts. The effects of this rare variant — mimicking the anticipated effects of drugs for lowering Apolipoprotein C3 —  were compared with a common variant of lipoprotein lipase (LPL). The findings suggest that the APOC3 variant has a wide range of actions on lipids and fatty acids. Much of the action of APOC3 on lipids is mediated via LPL action but a parallel intracellular mechanism might be relevant for the composition of VLDL particles. The results improve understanding of the role of APOC3 in triglyceride metabolism, its LPL independent action and elucidates the suitable as a new lipid-lowering target.

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