Zinc deficiency alters lipid metabolism in LDL receptor-deficient mice treated with rosiglitazone

Huiyun Shen, Ruth MacDonald, Dennis Bruemmer, Arnold Stromberg, Alan Daugherty, Xiang An Li, Michal J Toborek, Bernhard Hennig

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 languageEnglish
Pages (from-to)2339-2345
Number of pages7
JournalJournal of Nutrition
Volume137
Issue number11
StatePublished - Nov 1 2007
Externally publishedYes

Fingerprint

rosiglitazone
LDL Receptors
Lipid Metabolism
lipid metabolism
Zinc
zinc
receptors
mice
Peroxisome Proliferator-Activated Receptors
Fatty Acids
Fats
lipids

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

Shen, H., MacDonald, R., Bruemmer, D., Stromberg, A., Daugherty, A., Li, X. A., ... Hennig, B. (2007). Zinc deficiency alters lipid metabolism in LDL receptor-deficient mice treated with rosiglitazone. Journal of Nutrition, 137(11), 2339-2345.

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 journalArticle

Shen, H, MacDonald, R, Bruemmer, D, Stromberg, A, Daugherty, A, Li, XA, Toborek, MJ & Hennig, B 2007, 'Zinc deficiency alters lipid metabolism in LDL receptor-deficient mice treated with rosiglitazone', Journal of Nutrition, vol. 137, no. 11, pp. 2339-2345.
Shen H, MacDonald R, Bruemmer D, Stromberg A, Daugherty A, Li XA et al. Zinc deficiency alters lipid metabolism in LDL receptor-deficient mice treated with rosiglitazone. Journal of Nutrition. 2007 Nov 1;137(11):2339-2345.
Shen, Huiyun ; MacDonald, Ruth ; Bruemmer, Dennis ; Stromberg, Arnold ; Daugherty, Alan ; Li, Xiang An ; Toborek, Michal J ; Hennig, Bernhard. / Zinc deficiency alters lipid metabolism in LDL receptor-deficient mice treated with rosiglitazone. In: Journal of Nutrition. 2007 ; Vol. 137, No. 11. pp. 2339-2345.
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