title: Zinc deficiency increases plasma lipids and atherosclerotic markers in LDL-receptor-deficient mice.
abstract: Low zinc concentration can be associated with an increased risk of cardiovascular diseases. In the current study, we hypothesize that zinc deficiency can increase and zinc supplementation can decrease proatherosclerotic events in LDL receptor knock-out (LDL-R-/-) mice fed a moderate-fat diet. Mice were fed either a zinc-deficient (0 micromol Zn/g), a control (0.45 micromol Zn/g), or a zinc-supplemented (1.529 micromol Zn/g) diet for 4 wk. Mice fed the zinc-deficient diet had significantly increased concentrations of cholesterol and triacylglycerides in the VLDL and HDL fractions. Zinc supplementation decreased these lipid variables compared with control mice. We detected significantly higher concentrations of glutathione reductase mRNA in the thoracic aortae of zinc-deficient mice. Furthermore, inflammatory markers, such as nuclear factor-kappaB and vascular cell adhesion molecule-1, were significantly increased in zinc-deficient mice compared with mice of the control or supplemented groups. In addition, zinc deficiency significantly reduced the DNA binding activity of peroxisome proliferator activate receptors (PPARs) in liver extracts. Interestingly, mRNA expression levels of PPARgamma were significantly increased in thoracic aortae of zinc-deficient mice, indicating an adaptation process to decreased PPAR signaling. These data provide in vivo evidence of zinc deficiency inducing proinflammatory events in an atherogenic mouse model. These data also suggest that adequate zinc may be a critical component in protective PPAR signaling during atherosclerosis.
authors.affiliation: Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, 40546, USA.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Reiterer
authors.forename: Ruth
authors.initials: R
authors.lastname: MacDonald
authors.forename: Jim D
authors.initials: JD
authors.lastname: Browning
authors.forename: Jason
authors.initials: J
authors.lastname: Morrow
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Matveev
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
authors.forename: Eric
authors.initials: E
authors.lastname: Smart
authors.forename: Michal
authors.initials: M
authors.lastname: Toborek
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hennig
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D001835:Body Weight; D005980:Glutathione Reductase / Q000235:genetics; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009994:Osmolar Concentration; D047495:PPAR gamma / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency*; D014157:Transcription Factors / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008055:Lipids; D047495:PPAR gamma; D012333:RNA, Messenger; D011973:Receptors, LDL; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D005980:Glutathione Reductase; D015032:Zinc