Zinc deficiency alters lipid metabolism in LDL receptor deficient mice treated with rosiglitazone.
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 PPARgamma 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 PPARgamma 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.
Shen
Huiyun
H
Molecular and Cell Nutrition Laboratory, College of Agriculture, University of Kentucky, Lexington, KY 40536, USA.
MacDonald
Ruth
R
Bruemmer
Dennis
D
Stromberg
Arnold
A
Daugherty
Alan
A
Li
Xiang-an
XA
Toborek
Michal
M
Hennig
Bernhard
B
D000818:Animals; D002784:Cholesterol / Q000097:blood; D002149:Energy Intake; D005230:Fatty Acids, Nonesterified / Q000097:blood; D008055:Lipids / Q000502:physiology*; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011973:Receptors, LDL / Q000172:deficiency* / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D015032:Zinc / Q000172:deficiency* / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D008055:Lipids; D008074:Lipoproteins; D011973:Receptors, LDL; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002784:Cholesterol; D015032:Zinc