Pleiotropic effects of apolipoprotein C3 on HDL functionality and adipose tissue metabolic activity

J Lipid Res. 2017 Sep;58(9):1869-1883. doi: 10.1194/jlr.M077925. Epub 2017 Jul 12.


APOC3 is produced mainly by the liver and intestine and approximately half of plasma APOC3 associates with HDL. Though it was believed that APOC3 associates with HDL by simple binding to preexisting particles, recent data support that biogenesis of APOC3-containing HDL (APOC3-HDL) requires Abca1. Moreover, APOC3-HDL contributes to plasma triglyceride homeostasis by preventing APOC3 association with triglyceride-rich lipoproteins. Interestingly, APOC3-HDL also shows positive correlation with the morbidly obese phenotype. However, the roles of APOC3 in HDL functionality and adipose tissue metabolic activity remain unknown. Therefore, here we investigated the direct effects of APOC3 expression on HDL structure and function, as well as white adipose tissue (WAT) and brown adipose tissue (BAT) metabolic activity. C57BL/6 mice were infected with an adenovirus expressing human APOC3 or a recombinant attenuated control adenovirus expressing green fluorescent protein and blood and tissue samples were collected at 5 days postinfection. HDL was then analyzed for its apolipoprotein and lipid composition and particle functionality. Additionally, purified mitochondria from BAT and WAT were analyzed for uncoupling protein 1, cytochrome c (Cytc), and Cytc oxidase subunit 4 protein levels as an indirect measure of their metabolic activity. Serum metabolomic analysis was performed by NMR. Combined, our data show that APOC3 modulates HDL structure and function, while it selectively promotes BAT metabolic activation.

Keywords: brown adipose tissue; cholesterol efflux; high density lipoprotein; lipidomics; metabolomics; white adipose tissue.

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Adenoviridae / genetics
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / metabolism*
  • Animals
  • Antioxidants / metabolism
  • Apolipoprotein C-III / genetics*
  • Biological Transport / genetics
  • Cholesterol / metabolism
  • Energy Metabolism / genetics
  • Gene Transfer Techniques
  • Genetic Pleiotropy*
  • HEK293 Cells
  • Humans
  • Lipoproteins, HDL / metabolism*
  • Mice
  • Mitochondria / metabolism
  • Oxidative Phosphorylation
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / metabolism


  • Antioxidants
  • Apolipoprotein C-III
  • Lipoproteins, HDL
  • Tumor Necrosis Factor-alpha
  • Adenosine Triphosphate
  • Cholesterol