Abstract
Zinc is a structural and functional component of PPAR and zinc deficiency may be associated with an increased risk for cardiovascular diseases. We tested the hypothesis that zinc deficiency compromises lipid metabolism in rosiglitazone (RSG)-treated mice lacking the LDL-receptor (LDL-R) gene. LDL-R-deficient mice were maintained for 3 wk on low-fat (7 g/100 g) diets that were either zinc deficient or zinc adequate. Subsequently, diets were adjusted to a high-fat (HF) (15 g/100 g) regimen for 1 wk to produce a biological environment of mild oxidative and inflammatory stress. One-half of the mice within each zinc group was gavaged daily with the PPARg agonist RSG starting 2 d prior to the HF feeding. Selected lipid parameters were studied. Zinc deficiency increased plasma total cholesterol, which was also elevated by RSG. Zinc deficiency also caused an increased lipoprotein-cholesterol distribution toward the non-HDL fraction (VLDL, intermediate density lipoprotein, LDL). Plasma total fatty acids tended to increase during zinc deficiency and RSG treatment resulted in similar changes in the fatty acid profile in zinc-deficient mice. Fatty acid translocase (FAT/CD36) expression in abdominal aorta was upregulated by RSG only in zinc-deficient mice. In contrast, RSG treatment markedly increased lipoprotein lipase (LPL) expression only in zinc-adequate mice. In vitro studies confirmed that adequate zinc is required for RSG-induced PPARγ activity to transactivate target genes. These data suggest that in this atherogenic mouse model treated with RSG, lipid metabolism can be compromised during zinc deficiency and that adequate dietary zinc may be considered during therapy with the antidiabetic medicine RSG.
| Original language | English |
|---|---|
| Pages (from-to) | 2339-2345 |
| Number of pages | 7 |
| Journal | Journal of Nutrition |
| Volume | 137 |
| Issue number | 11 |
| State | Published - Nov 1 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Medicine (miscellaneous)
- Food Science
Cite this
Zinc deficiency alters lipid metabolism in LDL receptor-deficient mice treated with rosiglitazone. / Shen, Huiyun; MacDonald, Ruth; Bruemmer, Dennis; Stromberg, Arnold; Daugherty, Alan; Li, Xiang An; Toborek, Michal J; Hennig, Bernhard.
In: Journal of Nutrition, Vol. 137, No. 11, 01.11.2007, p. 2339-2345.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Zinc deficiency alters lipid metabolism in LDL receptor-deficient mice treated with rosiglitazone
AU - Shen, Huiyun
AU - MacDonald, Ruth
AU - Bruemmer, Dennis
AU - Stromberg, Arnold
AU - Daugherty, Alan
AU - Li, Xiang An
AU - Toborek, Michal J
AU - Hennig, Bernhard
PY - 2007/11/1
Y1 - 2007/11/1
N2 - Zinc is a structural and functional component of PPAR and zinc deficiency may be associated with an increased risk for cardiovascular diseases. We tested the hypothesis that zinc deficiency compromises lipid metabolism in rosiglitazone (RSG)-treated mice lacking the LDL-receptor (LDL-R) gene. LDL-R-deficient mice were maintained for 3 wk on low-fat (7 g/100 g) diets that were either zinc deficient or zinc adequate. Subsequently, diets were adjusted to a high-fat (HF) (15 g/100 g) regimen for 1 wk to produce a biological environment of mild oxidative and inflammatory stress. One-half of the mice within each zinc group was gavaged daily with the PPARg agonist RSG starting 2 d prior to the HF feeding. Selected lipid parameters were studied. Zinc deficiency increased plasma total cholesterol, which was also elevated by RSG. Zinc deficiency also caused an increased lipoprotein-cholesterol distribution toward the non-HDL fraction (VLDL, intermediate density lipoprotein, LDL). Plasma total fatty acids tended to increase during zinc deficiency and RSG treatment resulted in similar changes in the fatty acid profile in zinc-deficient mice. Fatty acid translocase (FAT/CD36) expression in abdominal aorta was upregulated by RSG only in zinc-deficient mice. In contrast, RSG treatment markedly increased lipoprotein lipase (LPL) expression only in zinc-adequate mice. In vitro studies confirmed that adequate zinc is required for RSG-induced PPARγ activity to transactivate target genes. These data suggest that in this atherogenic mouse model treated with RSG, lipid metabolism can be compromised during zinc deficiency and that adequate dietary zinc may be considered during therapy with the antidiabetic medicine RSG.
AB - Zinc is a structural and functional component of PPAR and zinc deficiency may be associated with an increased risk for cardiovascular diseases. We tested the hypothesis that zinc deficiency compromises lipid metabolism in rosiglitazone (RSG)-treated mice lacking the LDL-receptor (LDL-R) gene. LDL-R-deficient mice were maintained for 3 wk on low-fat (7 g/100 g) diets that were either zinc deficient or zinc adequate. Subsequently, diets were adjusted to a high-fat (HF) (15 g/100 g) regimen for 1 wk to produce a biological environment of mild oxidative and inflammatory stress. One-half of the mice within each zinc group was gavaged daily with the PPARg agonist RSG starting 2 d prior to the HF feeding. Selected lipid parameters were studied. Zinc deficiency increased plasma total cholesterol, which was also elevated by RSG. Zinc deficiency also caused an increased lipoprotein-cholesterol distribution toward the non-HDL fraction (VLDL, intermediate density lipoprotein, LDL). Plasma total fatty acids tended to increase during zinc deficiency and RSG treatment resulted in similar changes in the fatty acid profile in zinc-deficient mice. Fatty acid translocase (FAT/CD36) expression in abdominal aorta was upregulated by RSG only in zinc-deficient mice. In contrast, RSG treatment markedly increased lipoprotein lipase (LPL) expression only in zinc-adequate mice. In vitro studies confirmed that adequate zinc is required for RSG-induced PPARγ activity to transactivate target genes. These data suggest that in this atherogenic mouse model treated with RSG, lipid metabolism can be compromised during zinc deficiency and that adequate dietary zinc may be considered during therapy with the antidiabetic medicine RSG.
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UR - http://www.scopus.com/inward/citedby.url?scp=35848965463&partnerID=8YFLogxK
M3 - Article
C2 - 17951467
AN - SCOPUS:35848965463
VL - 137
SP - 2339
EP - 2345
JO - Journal of Nutrition
JF - Journal of Nutrition
SN - 0022-3166
IS - 11
ER -