The Journal of Lipid Research, the official lipidology journal of ASBMB, yesterday published our work on the "Pleiotropic effects of apolipoprotein C3 on HDL functionality and adipose tissue metabolic activity"

 

Apolipoprotein C3 (APOC3) is a small glycoprotein in blood, secreted by the liver and intestine. APOC3 plays important role in plasma triglyceride metabolism since numerous epidemiological and animal studies have established a direct correlation of plasma APOC3 levels to plasma triglyceride levels. Based on this important function of APOC3, silencing antisense oligonucleotides targeting Apoc3 expression are currently in clinical trials for the treatment of hypertriglyceridemia and its related pathologies.

 

In this paper we used adenovirus mediated gene transfer of APOC3 to mice in order to study how increased blood levels of this protein may affect HDL particle composition and functionality and adipose tissue metabolic activation. Our findings demonstrate that APOC3 stimulates oxidative phosphorylation towards ATP production selectively in Brown Adipose Tissue (BAT), thus promoting fat burning and weight loss. Moreover, APOC3 alters apolipoprotein and lipid composition of HDL, triggering distinct changes in its properties and functionality.

The study is important because more than 30 years since human Apoc3 nucleotide sequence was identified, our knowledge of APOC3 functions in relation to human health and disease still remains limited. The sole most widely accepted function of APOC3 is in atherosclerosis and more precisely in the regulation of plasma triglyceride levels through inhibition of plasma Lpl activity and catabolism of triglyceride-rich lipoproteins. Therefore, in contrast to the previous view identifying APOC3 as solely detrimental to human health, here we found that it also possesses some very important properties, which should not be ignored in the designing of new pharmaceuticals aiming at APOC3.

Apparently, APOC3 is another example of the ancient Greek saying “μέτρον άριστον” (everything in moderation). Based on the finding that reducing APOC3 levels to physiological may be beneficial for the treatment of some forms of hypertriglyceridemia, complete silencing of its expression may adversely affect other physiological processes, crucial for human health.

I would like to thank all study participants for their contribution to this interesting work.

To read the paper please go to https://www.ncbi.nlm.nih.gov/pubmed/28701354