|| Checking for direct PDF access through Ovid
Butyrate is a short chain fatty acid, formed by fermentation in the large intestine, with a well-known anti-inflammatory property. As inflammation plays a key role in atherogenesis and insulin resistance, we studied the effects of butyrate supplementation on atherosclerosis and glucose homeostasis. ApoE-deficient mice received control diet (CT, n=8) or 1% butyrate supplemented diet (BUT, n=8) for 10 weeks. Oral glucose tolerance test (OGTT), insulin sensitivity test (IST), lipid profile and fasting glucose were evaluated. Atherosclerosis lesion area was studied in two sites, aorta and aortic root. In the latter, CCL2, VCAM-1, collagen, and matrix metalloproteinase-2 (MMP-2) were also assessed. In order to confirm the in vivo data, culture of human endothelial cells (E.A. Hy926) were pre-incubated with butyrate (0.5 or 1.0mM) and stimulated with oxidized LDL (oxLDL) for 4h for CCL2 and VCAM-1 evaluation by immunofluorescence. Lipid profile, fasting glucose and OGTT were similar between groups. Insulin sensitivity was improved in BUT group mice. Butyrate-treated mice showed reduction in the aorta atherosclerosis lesion (CT=4.1%, BUT=1.8%; percentage of the surface area). Despite of similar lesion area in the BUT- treated mice aortic roots presented reduced inflammation-related molecules, CCL2 (CT=0.25FI, BUT=1.2FI) and VCAM-1(CT=0.42FI, BUT=013FI), and improvement on plaque stability with reduced MMP2 (CT=0.51FI, BUT=0.13FI) and increased collagen (CT=0.19FI, BUT=0.44FI). These results suggest that aortic root lesion areas were similar probably due to a more stable and thicker fibrous cap in the BUT group (beneficial factor). The production of VCAM-1 and CCL2 by butyrate pretreated endothelial cells was reduced compared to control cells, suggesting that butyrate reduces leukocyte migration toward lesion reducing atherogenesis. In conclusion our data show that butyrate supplementation ameliorates atherosclerosis due to the anti-inflammatory effect and increased plaque stability.