Zinc Deficiency Augments Leptin Production and Exacerbates Macrophage Infiltration into Adipose Tissue in Mice Fed a High-Fat Diet
Zinc Deficiency Augments Leptin Production and Exacerbates Macrophage Infiltration into Adipose Tissue in Mice Fed a High-Fat Diet
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DOI：
10.3945/jn.113.175158
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发表时间：
2013-07-01
影响因子：
4.2
通讯作者：
Knoell, Daren L.
中科院分区：
文献类型：
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作者：
Liu, Ming-Jie;Bao, Shengying;Knoell, Daren L.
锌（Zn）缺乏和肥胖是全球公共卫生问题。缺锌与肥胖和胰岛素抵抗和 2 型糖尿病等合并症有关。然而，锌在肥胖中的作用仍不清楚。使用高脂肪和低锌摄入量（0.5-1.5 mg/kg）相结合的小鼠模型，我们研究了锌缺乏是否会加剧肥胖程度以及代谢和免疫功能的扰动。 C57BL16 小鼠被随机分配接受高脂肪饮食 (HFD) 或对照 (C) 饮食 6 周，然后进一步细分为另外 2 个组，分别喂食缺锌饮食（C-Zn、HFD-Zn），以及 C 饮食和 HFD，持续 3 周（n = 8-9 只小鼠/组）。内脏脂肪、胰岛素抵抗或全身炎症的程度不受缺锌的影响。引人注目的是，缺锌显着增加了肥胖小鼠肝脏中的循环瘦素浓度（HFD-Zn 与 HFD：分别为 3.15 +/- 0.16 与 2.59 +/- 0.12 μg/L）和瘦素信号传导。此外，CD68 蛋白分析证实，HFD-Zn 组脂肪组织中巨噬细胞特异性标记物 ADAM8（包含解整合素和金属蛋白酶结构域的蛋白 8）和 CD68（分化簇 68）的基因表达显着高于 HFD 组，表明巨噬细胞浸润增加。对脂肪组织中所有锌转运蛋白的锌含量和 mRNA 谱的检查揭示了锌代谢对肥胖和锌缺乏的改变。我们的结果表明，锌缺乏会增加肥胖小鼠瘦素的产生，并加剧巨噬细胞对脂肪组织的浸润，表明锌在肥胖代谢和免疫失调中的重要性。
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. C57BL16 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 mu g/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.