Inside cells, lipids are stored within micelles known as cytosolic lipid droplets (LDs). PLIN2, belonging to LD-coating protein family, is expressed in several non-adipose tissues, including liver, skeletal muscle, endothelial cells macrophages, pancreatic b cells, mammary gland, gonads, heart, and gut enterocytes.
PLIN2 is considered a marker of LD accumulation under both physiological and pathological conditions. Recent studies have shown that PLIN2 is an important key factor in the pathogenesis of atherosclerosis. Expression of PLIN2 mRNA has also been demonstrated in human atherosclerotic lesions by in situ hybridization experiments.
Type 2 Diabetes (T2D) is a major cardiovascular risk factor contributing to cardiovascular complications by inducing vascular cell dysfunction.
Metformin is one of the most common treatments for T2D, improving insulin sensitivity, decreasing hepatic gluconeogenesis, promoting glucose uptake into muscles and increasing fatty acid oxidation in adipose tissue. In a previous study, Fang and collaborators found that metformin significantly decreased the expression levels of PLIN2 in liver suggesting a role of PLIN2 in preventing hepatic steatosis.
Aim of this study will be to investigate PLIN2 expression in circulating monocytes from T2D patients with and without metformin treatment, and in subjects without T2D as controls.
Furthermore, we will evaluate how metformin treatment acting on PLIN2 expression modulates the pro-inflammatory cytokines expression pattern.
Data of this study will provide evidences for one of the mechanisms through which metformin inhibits inflammation in atherosclerosis by PLIN2 targeting.
Furthermore, these results may underline PLIN2 as a key target in the treatment of inflammation during atherosclerosis.
Previous studies have investigated the impact of T2D on PLIN2 expression and localization in human ß-cells, myotubes and hepatocytes. Until now, data highlighting the mechanisms modulating PLIN2 expression in monocytes from T2D patients on treatment with metformin are missing. Lipid droplets accumulation in macrophages alters its biology and enhances PLIN2 expression but metformin treatment significantly decreases the expression levels of PLIN2 in murine primary hepatocytes suggesting a role of PLIN2 in the metformin-mediated regulation of hepatic steatosis.
We expect that metformin treatment prevents the development of an inflammatory state and a pro-atherosclerotic condition in monocytes of T2D subjects by downregulating PLIN2 expression.
If so, our data will provide one mechanism through which metformin inhibits inflammation in atherosclerosis by PLIN2 targeting.
Furthermore, these results may underline PLIN2 as a key target in the treatment of inflammation during atherosclerosis.