title: The nitroxide radical TEMPOL prevents obesity, hyperlipidaemia, elevation of inflammatory cytokines, and modulates atherosclerotic plaque composition in apoE-/- mice.
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.
authors.affiliation: Free Radical Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia; Faculty of Medicine, University of Sydney, NSW 2006, Australia. Electronic address: christinehjkim@gmail.com.
authors.forename: Christine H J
authors.initials: CH
authors.lastname: Kim
authors.affiliation: National Cancer Institute, Radiation Biology Branch, Center for Cancer Research, Building 10, Room B3-B69, Bethesda, MD 20892, USA. Electronic address: jbm@helix.nih.gov.
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.affiliation: Faculty of Medicine, University of Sydney, NSW 2006, Australia; Immunobiology Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia. Electronic address: bursillc@hri.org.au.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Bursill
authors.affiliation: National Cancer Institute, Radiation Biology Branch, Center for Cancer Research, Building 10, Room B3-B69, Bethesda, MD 20892, USA. Electronic address: stasia@mail.nih.gov.
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Sowers
authors.affiliation: National Cancer Institute, Radiation Biology Branch, Center for Cancer Research, Building 10, Room B3-B69, Bethesda, MD 20892, USA. Electronic address: thetforda@mail.nih.gov.
authors.forename: Angela
authors.initials: A
authors.lastname: Thetford
authors.affiliation: National Cancer Institute, Radiation Biology Branch, Center for Cancer Research, Building 10, Room B3-B69, Bethesda, MD 20892, USA. Electronic address: cook@helix.nih.gov.
authors.forename: John A
authors.initials: JA
authors.lastname: Cook
authors.affiliation: Faculty of Science, University of Technology Sydney, PO Box 123, Broadway, NSW 2007, Australia. Electronic address: david.vanreyk@uts.edu.au.
authors.forename: David M
authors.initials: DM
authors.lastname: van Reyk
authors.affiliation: Free 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. Electronic address: davies@sund.ku.dk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood*; D018345:Mice, Knockout; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D058226:Plaque, Atherosclerotic; D013113:Spin Labels; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D000890:Anti-Infective Agents; D019440:Anti-Obesity Agents; D000975:Antioxidants; D001057:Apolipoproteins E; D015415:Biomarkers; D003497:Cyclic N-Oxides; D016207:Cytokines; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D013113:Spin Labels; D014280:Triglycerides; D002784:Cholesterol; C001803:tempol
keywords: Adipokines; Atherosclerosis; Cardiovascular disease; Inflammatory cytokines; Lipid; Nitroxide; TEMPOL
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