The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE^-/- mice

© 2015 Elsevier Ireland Ltd. 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 10mg/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.