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

Abstract

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.

Apolipoprotein CIII and diabetes. Is there a link?

“…Recent studies showed that the formation of HDL‐ApoCIII is a result of the interaction of ApoCIII with the lipid transporter ATP‐biding cassette subtype A1 (ABCA1), rather than a simple binding of ApoCIII to pre‐existing HDL particles . Interestingly, the presence of ApoCIII on HDL is accompanied by qualitative and morphological changes of HDL particles . In a clinical trial of morbidly obese individuals, HDL was isolated from plasma the day before and 6 months following bariatric surgery .…”

“…87 Interestingly, the presence of ApoCIII on HDL is accompanied by qualitative and morphological changes of HDL particles. 88 In a clinical trial of morbidly obese individuals, HDL was isolated from plasma the day before and 6 months following bariatric surgery. 89 A dramatic increase in the ApoAI/ApoCIII and ApoAI/ApoE ratios in HDL particles was observed, accompanied by a significant improvement in the antioxidant potential of HDL and a shift towards more mature HDL particles.…”

Simultaneous LC/MS/MS quantification of eight apolipoproteins in normal and hypercholesterolemic mouse plasma

“…Moreover, several apolipoproteins have been associated with metabolic functions in glucose homeostasis, insulin sensitivity, and adipose tissue biology and may thus contribute to obesity and diabetes mellitus (9)(10)(11)(12). It is also established that apolipoproteins, such as apoJ and, in particular, apoE, contribute to the pathogenesis of Alzheimer's disease via multiple mechanisms (13)(14)(15) and that apolipoproteins can exhibit antiinflammatory and antioxidative functions (16)(17)(18).…”

Predicting biomarkers from classifier for liver metastasis of colorectal adenocarcinomas using machine learning models

“…40 Apolipoprotein C3 (APOC3) is a glycoprotein secreted by the liver and intestines, the expression of which is positively related to energy expenditure and energy demand by participating in the plasma triglyceride metabolism. 41 Similarly, the increasing quartiles of ApoB-100 and triglycerides are positively associated with the risk of CRC. 42 In addition, the increased APOB/APOA1 ratio is related to the nodal metastasis of CRC.…”