Faculty of Pharmaceutical Science, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima City 770-8514, Japan.
Toxicol Appl Pharmacol. 2012 Jan 1;258(1):32-42. doi: 10.1016/j.taap.2011.10.004. Epub 2011 Oct 12.
Metals and metalloid species are involved in homeostasis in energy systems such as glucose metabolism. Enlarged adipocytes are one of the most important causes of obesity-associated diseases. In this study, we studied the possibility that various metals, namely, CoCl(2), HgCl(2), NaAsO(2) and MnCl(2) pose risk to or have beneficial effects on white adipose tissue (WAT). Exposure to the four metals resulted in decreases in WAT weight and the size of enlarged adipocytes in mice fed a high-fat diet (HFD) without changes in liver weight, suggesting that the size and function of adipocytes are sensitive to metals. Repeated administration of CoCl(2) significantly increased serum leptin, adiponectin and high-density lipoprotein (HDL) cholesterol levels and normalized glucose level and adipose cell size in mice fed HFD. In contrast, HgCl(2) treatment significantly decreased serum leptin level with the down-regulation of leptin mRNA expression in WAT and a reduction in adipocyte size. Next, we tried to investigate possible factors that affect adipocyte size. Repeated exposure to HgCl(2) significantly decreased the expression levels of factors upon the regulation of energy such as the PPARα and PPARγ mRNA expression levels in adipocytes, whereas CoCl(2) had little effect on those genes expressions compared with that in the case of the mice fed HFD with a vehicle. In addition, repeated administration of CoCl(2) enhanced AMPK activation in a dose-dependent manner in the liver, skeletal muscle and WAT; HgCl(2) treatment also enhanced AMPK activation in the liver. Thus, both Co and Hg reduced WAT weight and the size of enlarged adipocytes, possibly mediated by AMKP activation in the mice fed HFD. However, inorganic cobalt may have a preventive role in obesity-related diseases through increased leptin, adiponectin and HDL-cholesterol levels, whereas inorganic mercury may accelerate the development of such diseases. These results may lead to the development of new approaches to establishing the role of metals in adipose tissue of obesity-related diseases.
金属和类金属参与能量系统如葡萄糖代谢的体内平衡。肥大的脂肪细胞是肥胖相关疾病的最重要原因之一。在这项研究中，我们研究了各种金属，即 CoCl2、HgCl2、NaAsO2 和 MnCl2，对白色脂肪组织（WAT）是否有风险或有益。暴露于这四种金属会导致高脂饮食（HFD）喂养的小鼠的 WAT 重量和肥大脂肪细胞的大小减少，而肝脏重量没有变化，这表明脂肪细胞的大小和功能对金属很敏感。重复给予 CoCl2 可显著增加血清瘦素、脂联素和高密度脂蛋白（HDL）胆固醇水平，并使 HFD 喂养的小鼠的血糖水平和脂肪细胞大小正常化。相比之下，HgCl2 处理可显著降低血清瘦素水平，同时下调 WAT 中的瘦素 mRNA 表达并减少脂肪细胞大小。接下来，我们试图研究可能影响脂肪细胞大小的因素。重复暴露于 HgCl2 可显著降低脂肪细胞中能量调节因子的表达水平，如 PPARα 和 PPARγ mRNA 表达水平，而 CoCl2 对这些基因的表达水平几乎没有影响，与 HFD 喂养的小鼠相比。此外，重复给予 CoCl2 可在剂量依赖性方式增强肝脏、骨骼肌和 WAT 中的 AMPK 激活；HgCl2 处理也可增强肝脏中的 AMPK 激活。因此，Co 和 Hg 均可通过激活 AMPK 来减少 HFD 喂养的小鼠的 WAT 重量和肥大脂肪细胞的大小。然而，无机钴可能通过增加瘦素、脂联素和 HDL-胆固醇水平来预防肥胖相关疾病，而无机汞可能会加速这些疾病的发展。这些结果可能会导致开发新方法来确定金属在肥胖相关疾病的脂肪组织中的作用。
