Highlights
- •Nitroxides scavenge radicals, are superoxide dismutase mimics and enzyme inhibitors.
- •Apo E−/− mice were fed a high fat diet without or with the nitroxide TEMPOL.
- •TEMPOL increased leptin and decreased obesity, adiponectin, plasma lipids and cytokines.
- •Plaque collagen and macrophage numbers were increased, and lipid levels decreased.
- •TEMPOL suppresses metabolic changes and increases atherosclerotic plaque stability.
Abstract
Objective
The nitroxide compound TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl radical) has been shown to prevent obesity-induced changes in adipokines in
cell and animal systems. In this study we investigated whether supplementation with
TEMPOL inhibits inflammation and atherosclerosis in apoE−/− mice fed a high fat diet (HFD).
Methods
ApoE−/− mice were fed for 12 weeks on standard chow diet or a high-fat diet. Half the mice
were supplemented with 10 mg/g TEMPOL in their food. Plasma samples were analysed
for triglycerides, cholesterol, low- and high-density lipoprotein cholesterol, inflammatory
cytokines and markers (interleukin-6, IL-6; monocyte-chemotactic protein, MCP-1; myeloperoxidase,
MPO; serum amyloid A, SAA; adiponectin; leptin). Plaques in the aortic sinus were
analysed for area, and content of collagen, lipid, macrophages and smooth muscle cells.
Results
High fat feeding resulted in marked increases in body mass and plasma lipid levels.
Dietary TEMPOL decreased both parameters. In the high-fat-fed mice significant elevations
in plasma lipid levels and the inflammatory markers IL-6, MCP-1, MPO, SAA were detected,
along with an increase in leptin and a decrease in adiponectin. TEMPOL supplementation
reversed these effects. When compared to HFD-fed mice, TEMPOL supplementation increased
plaque collagen content, decreased lipid content and increased macrophage numbers.
Conclusions
These data indicate that in a well-established model of obesity-associated hyperlipidaemia
and atherosclerosis, TEMPOL had a significant impact on body mass, atherosclerosis,
hyperlipidaemia and inflammation. TEMPOL may therefore be of value in suppressing
obesity, metabolic disorders and increasing atherosclerotic plaque stability.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 17, 2015
Accepted:
March 8,
2015
Received in revised form:
January 21,
2015
Received:
June 16,
2014
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
