TEMPOL had a significant positive impact on body mass, atherosclerosis, hyperlipidaemia and inflammation
Atherosclerosis. 2015 May;240(1):234-41.
The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE(-/-) mice.
Kim CH1, Mitchell JB2, Bursill CA3, Sowers AL4, Thetford A5, Cook JA6, van Reyk DM7, Davies MJ8.
1Free Radical Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; Faculty of Medicine, University of Sydney, NSW 2006, Australia.
2National Cancer Institute, Radiation Biology Branch, Center for Cancer Research, Building 10, Room B3-B69, Bethesda, MD 20892, USA.
3Faculty of Medicine, University of Sydney, NSW 2006, Australia; Immunobiology Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia.
4National Cancer Institute, Radiation Biology Branch, Center for Cancer Research, Building 10, Room B3-B69, Bethesda, MD 20892, USA.
5National Cancer Institute, Radiation Biology Branch, Center for Cancer Research, Building 10, Room B3-B69, Bethesda, MD 20892, USA.
6National Cancer Institute, Radiation Biology Branch, Center for Cancer Research, Building 10, Room B3-B69, Bethesda, MD 20892, USA.
7Faculty of Science, University of Technology Sydney, PO Box 123, Broadway, NSW 2007, Australia.
8Free Radical Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; Faculty of Medicine, University of Sydney, NSW 2006, Australia; Department of Biomedical Sciences, Building 4.5, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
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.
