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Anti‐atherosclerotic Properties of PPARγ are Dysfunctional During Zinc Deficiency in LDL‐R−/− Mice Treated with Rosiglitazone
Author(s) -
Shen Huiyun,
MacDonald Ruth,
Stromberg Arnold,
Daugherty Alan,
Li XiangAn,
Toborek Michal,
Hennig Bernhard
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a719-d
Subject(s) - rosiglitazone , medicine , endocrinology , cd36 , zinc deficiency (plant disorder) , inflammation , peroxisome proliferator activated receptor , ppar agonist , insulin , zinc , chemistry , receptor , organic chemistry
Low zinc concentrations may be associated with an increased risk of cardiovascular diseases. We tested the hypothesis that anti‐atherogenic properties of PPARγ are compromised during zinc‐deficiency in rosiglitazone (RSG)‐treated LDL‐R−/− mice. The mice were maintained for 4 weeks on zinc deficient (ZD) or adequate (ZA) diets. Half of the mice were gavaged with the PPARγ agonist RSG. Subsequently, selected inflammation and lipid parameters were studied. RSG treatment decreased plasma insulin levels only in ZA mice. iNOS gene expression in abdominal aorta was down‐regulated by RSG only in ZA mice. MCP‐1 was induced by RSG only during ZD. RSG tended to increase anti‐inflammatory cytokine levels in plasma of ZA but not ZD mice. Plasma IL‐6 levels were increased by RSG during ZD. RSG treatment decreased plasma IL‐12 levels in ZA mice, whereas opposite effects were observed during ZD. RSG treatment contributed to a proatherogenic lipoprotein‐cholesterol profile only in ZD mice. CD36 expression in abdominal aorta and plasma fatty acids were increased by RSG only in ZD mice. In contrast, RSG treatment increased LPL expression only in ZA mice. These data suggest that in this atherosclerotic mouse model PPARγ signaling was compromised during ZD and that adequate dietary zinc is critical for proper function of the anti‐diabetic medicine rosiglitazone. (Supported by grants from NIEHS/NIH, USDA/NRI, NCBA, KCA and KY AES).