Format

Send to

Choose Destination
Br J Nutr. 2015 Jun 14;113(11):1704-11. doi: 10.1017/S0007114515001117. Epub 2015 Apr 16.

Long-term high fat feeding of rats results in increased numbers of circulating microvesicles with pro-inflammatory effects on endothelial cells.

Author information

1
Department of Comparative Biomedical Sciences,Royal Veterinary College,Royal College Street,LondonNW1 0TU,UK.

Abstract

Obesity and type 2 diabetes lead to dramatically increased risks of atherosclerosis and CHD. Multiple mechanisms converge to promote atherosclerosis by increasing endothelial oxidative stress and up-regulating expression of pro-inflammatory molecules. Microvesicles (MV) are small ( < 1 μm) circulating particles that transport proteins and genetic material, through which they are able to mediate cell-cell communication and influence gene expression. Since MV are increased in plasma of obese, insulin-resistant and diabetic individuals, who often exhibit chronic vascular inflammation, and long-term feeding of a high-fat diet (HFD) to rats is a well-described model of obesity and insulin resistance, we hypothesised that this may be a useful model to study the impact of MV on endothelial inflammation. The number and cellular origin of MV from HFD-fed obese rats were characterised by flow cytometry. Total MV were significantly increased after feeding HFD compared to feeding chow (P< 0·001), with significantly elevated numbers of MV derived from leucocyte, endothelial and platelet compartments (P< 0·01 for each cell type). MV were isolated from plasma and their ability to induce reactive oxygen species (ROS) formation and vascular cell adhesion molecule (VCAM)-1 expression was measured in primary rat cardiac endothelial cells in vitro. MV from HFD-fed rats induced significant ROS (P< 0·001) and VCAM-1 expression (P= 0·0275), indicative of a pro-inflammatory MV phenotype in this model of obesity. These findings confirm that this is a useful model to further study the mechanisms by which diet can influence MV release and subsequent effects on cardio-metabolic health.

KEYWORDS:

Endothelium; Extracellular vesicles; Inflammation; Microvesicles; Obesity; Oxidative stress; Vascular cell adhesion molecule-1

PMID:
25880162
DOI:
10.1017/S0007114515001117
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Cambridge University Press
Loading ...
Support Center