Zinc deficiency augments leptin production and exacerbates macrophage infiltration into adipose tissue in mice fed a high-fat diet

Ming Jie Liu, Shengying Bao, Eric R. Bolin, Dara L. Burris, Xiaohua Xu, Qinghua Sun, David W. Killilea, Qiwen Shen, Ouliana Ziouzenkova, Martha A. Belury, Mark L. Failla, Daren L Knoell

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Abstract

Zinc (Zn) deficiency and obesity are global public health problems. Zn deficiency is associated with obesity and comorbid conditions that include insulin resistance and type 2 diabetes. However, the function of Zn in obesity remains unclear. Using a mouse model of combined high-fat and low-Zn intake (0.5-1.5 mg/kg), we investigated whether Zn deficiency exacerbates the extent of adiposity as well as perturbations in metabolic and immune function. C57BL/6 mice were randomly assigned to receive either a high-fat diet (HFD) or a control (C) diet for 6 wk, followed by further subdivision into 2 additional groups fed Zn-deficient diets (C-Zn, HFD-Zn), along with a C diet and an HFD, for 3 wk (n = 8-9 mice/group). The extent of visceral fat, insulin resistance, or systemic inflammation was unaffected by Zn deficiency. Strikingly, Zn deficiency significantly augmented circulating leptin concentrations (HFD-Zn vs. HFD: 3.15 ± 0.16 vs. 2.59 ± 0.12 μg/L, respectively) and leptin signaling in the liver of obese mice. Furthermore, gene expression of macrophage-specific markers ADAM8 (A disintegrin and metalloproteinase domain-containing protein 8) and CD68 (cluster of differentiation 68) was significantly greater in adipose tissue in the HFD-Zn group than in the HFD group, as confirmed by CD68 protein analysis, indicative of increased macrophage infiltration. Inspection of Zn content and mRNA profiles of all Zn transporters in the adipose tissue revealed alterations of Zn metabolism to obesity and Zn deficiency. Our results demonstrate that Zn deficiency increases leptin production and exacerbates macrophage infiltration into adipose tissue in obese mice, indicating the importance of Zn in metabolic and immune dysregulation in obesity.

Original languageEnglish (US)
Pages (from-to)1036-1045
Number of pages10
JournalJournal of Nutrition
Volume143
Issue number7
DOIs
StatePublished - Jul 1 2013

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High Fat Diet
Leptin
Adipose Tissue
Zinc
Macrophages
Obesity
Obese Mice
Diet
Insulin Resistance
Disintegrins
Intra-Abdominal Fat
Adiposity
Metalloproteases
Inbred C57BL Mouse
Type 2 Diabetes Mellitus

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Zinc deficiency augments leptin production and exacerbates macrophage infiltration into adipose tissue in mice fed a high-fat diet. / Liu, Ming Jie; Bao, Shengying; Bolin, Eric R.; Burris, Dara L.; Xu, Xiaohua; Sun, Qinghua; Killilea, David W.; Shen, Qiwen; Ziouzenkova, Ouliana; Belury, Martha A.; Failla, Mark L.; Knoell, Daren L.

In: Journal of Nutrition, Vol. 143, No. 7, 01.07.2013, p. 1036-1045.

Research output: Contribution to journalArticle

Liu, MJ, Bao, S, Bolin, ER, Burris, DL, Xu, X, Sun, Q, Killilea, DW, Shen, Q, Ziouzenkova, O, Belury, MA, Failla, ML & Knoell, DL 2013, 'Zinc deficiency augments leptin production and exacerbates macrophage infiltration into adipose tissue in mice fed a high-fat diet', Journal of Nutrition, vol. 143, no. 7, pp. 1036-1045. https://doi.org/10.3945/jn.113.175158
Liu, Ming Jie ; Bao, Shengying ; Bolin, Eric R. ; Burris, Dara L. ; Xu, Xiaohua ; Sun, Qinghua ; Killilea, David W. ; Shen, Qiwen ; Ziouzenkova, Ouliana ; Belury, Martha A. ; Failla, Mark L. ; Knoell, Daren L. / Zinc deficiency augments leptin production and exacerbates macrophage infiltration into adipose tissue in mice fed a high-fat diet. In: Journal of Nutrition. 2013 ; Vol. 143, No. 7. pp. 1036-1045.
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abstract = "Zinc (Zn) deficiency and obesity are global public health problems. Zn deficiency is associated with obesity and comorbid conditions that include insulin resistance and type 2 diabetes. However, the function of Zn in obesity remains unclear. Using a mouse model of combined high-fat and low-Zn intake (0.5-1.5 mg/kg), we investigated whether Zn deficiency exacerbates the extent of adiposity as well as perturbations in metabolic and immune function. C57BL/6 mice were randomly assigned to receive either a high-fat diet (HFD) or a control (C) diet for 6 wk, followed by further subdivision into 2 additional groups fed Zn-deficient diets (C-Zn, HFD-Zn), along with a C diet and an HFD, for 3 wk (n = 8-9 mice/group). The extent of visceral fat, insulin resistance, or systemic inflammation was unaffected by Zn deficiency. Strikingly, Zn deficiency significantly augmented circulating leptin concentrations (HFD-Zn vs. HFD: 3.15 ± 0.16 vs. 2.59 ± 0.12 μg/L, respectively) and leptin signaling in the liver of obese mice. Furthermore, gene expression of macrophage-specific markers ADAM8 (A disintegrin and metalloproteinase domain-containing protein 8) and CD68 (cluster of differentiation 68) was significantly greater in adipose tissue in the HFD-Zn group than in the HFD group, as confirmed by CD68 protein analysis, indicative of increased macrophage infiltration. Inspection of Zn content and mRNA profiles of all Zn transporters in the adipose tissue revealed alterations of Zn metabolism to obesity and Zn deficiency. Our results demonstrate that Zn deficiency increases leptin production and exacerbates macrophage infiltration into adipose tissue in obese mice, indicating the importance of Zn in metabolic and immune dysregulation in obesity.",
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AU - Liu, Ming Jie

AU - Bao, Shengying

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AU - Burris, Dara L.

AU - Xu, Xiaohua

AU - Sun, Qinghua

AU - Killilea, David W.

AU - Shen, Qiwen

AU - Ziouzenkova, Ouliana

AU - Belury, Martha A.

AU - Failla, Mark L.

AU - Knoell, Daren L

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N2 - Zinc (Zn) deficiency and obesity are global public health problems. Zn deficiency is associated with obesity and comorbid conditions that include insulin resistance and type 2 diabetes. However, the function of Zn in obesity remains unclear. Using a mouse model of combined high-fat and low-Zn intake (0.5-1.5 mg/kg), we investigated whether Zn deficiency exacerbates the extent of adiposity as well as perturbations in metabolic and immune function. C57BL/6 mice were randomly assigned to receive either a high-fat diet (HFD) or a control (C) diet for 6 wk, followed by further subdivision into 2 additional groups fed Zn-deficient diets (C-Zn, HFD-Zn), along with a C diet and an HFD, for 3 wk (n = 8-9 mice/group). The extent of visceral fat, insulin resistance, or systemic inflammation was unaffected by Zn deficiency. Strikingly, Zn deficiency significantly augmented circulating leptin concentrations (HFD-Zn vs. HFD: 3.15 ± 0.16 vs. 2.59 ± 0.12 μg/L, respectively) and leptin signaling in the liver of obese mice. Furthermore, gene expression of macrophage-specific markers ADAM8 (A disintegrin and metalloproteinase domain-containing protein 8) and CD68 (cluster of differentiation 68) was significantly greater in adipose tissue in the HFD-Zn group than in the HFD group, as confirmed by CD68 protein analysis, indicative of increased macrophage infiltration. Inspection of Zn content and mRNA profiles of all Zn transporters in the adipose tissue revealed alterations of Zn metabolism to obesity and Zn deficiency. Our results demonstrate that Zn deficiency increases leptin production and exacerbates macrophage infiltration into adipose tissue in obese mice, indicating the importance of Zn in metabolic and immune dysregulation in obesity.

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