Liu Zao-Ling, Jiang Shu-Rui, Fan Yong, Wang Jia-Sui, Wang Meng-Lin, Li Mei-Yan
School of Public Health, Xinjiang Medical University, Xinjiang, China.
The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China.
J Chin Med Assoc. 2023 Apr 1;86(4):388-398. doi: 10.1097/JCMA.0000000000000886. Epub 2023 Jan 23.
Environmental polybrominated diphenyl ether (PBDE) exposure may be associated with diabetes and obesity. 2,2',4,4',5,5'-Hexabromodiphenyl ether (BDE-153) is one of the most abundant and widely distributed homologs of PBDEs detected in humans. This study investigated the effects of BDE-153 on the expression of adipokines and glucose and lipid metabolism.
Adult male C57BL/6 mice were divided into five BDE-153 groups and one control group. After BDE-153 exposure for 4 weeks, the levels of biochemical indexes and the mRNA and protein expression levels of leptin, adiponectin, peroxisome proliferators activated receptors gamma (PPARγ), and AMPKα were measured. The histomorphological changes of liver and pancreas tissues were observed.
After BDE-153 exposure, the weight of mice in the medium-high-dose group at different exposure times was lower than that in the control group ( p all <0.05), and the body weight decreased slightly with the increase of the dose of BDE-153. BDE-153 caused the disorder of glucose and lipid metabolism in mice, the weight of liver and pancreas increased, lipid droplets accumulated in liver cells, and the positive rate of insulin staining increased in a dose-dependent manner. BDE-153 also interfered with the expression of PPARγ, AMPKα, and adipokines. The results of restrictive cubic splines (RCS) showed that there were a nonlinear dose-response relationship between the exposure dose of BDE-153 and the expression levels of PPARγ, AMPKα, and adipokines.
Our results suggest that BDE-153 may interfere with the expression of adipokines and the secretion of insulin by affecting the expression of PPARγ and AMPKα, which play a key role in glucose and lipid metabolism, leading to the occurrence of glucose and lipid metabolism disorder.
环境多溴二苯醚（PBDE）暴露可能与糖尿病和肥胖症有关。2,2',4,4',5,5'-六溴二苯醚（BDE-153）是在人体中检测到的多溴二苯醚中含量最高、分布最广的同系物之一。本研究调查了BDE-153对脂肪因子表达以及葡萄糖和脂质代谢的影响。
将成年雄性C57BL/6小鼠分为五个BDE-153组和一个对照组。BDE-153暴露4周后，测量生化指标水平以及瘦素、脂联素、过氧化物酶体增殖物激活受体γ（PPARγ）和AMPKα的mRNA和蛋白表达水平。观察肝脏和胰腺组织的组织形态学变化。
BDE-153暴露后，不同暴露时间的中高剂量组小鼠体重低于对照组（所有p<0.05），且体重随BDE-153剂量增加略有下降。BDE-153导致小鼠葡萄糖和脂质代谢紊乱，肝脏和胰腺重量增加，肝细胞内脂滴积累，胰岛素染色阳性率呈剂量依赖性增加。BDE-153还干扰了PPARγ、AMPKα和脂肪因子的表达。限制性立方样条（RCS）结果表明，BDE-153暴露剂量与PPARγ、AMPKα和脂肪因子表达水平之间存在非线性剂量反应关系。
我们的结果表明，BDE-153可能通过影响在葡萄糖和脂质代谢中起关键作用的PPARγ和AMPKα的表达，干扰脂肪因子的表达和胰岛素的分泌，导致葡萄糖和脂质代谢紊乱的发生。
