Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Aug 15, 2021; 12(8): 1267-1281
Published online Aug 15, 2021. doi: 10.4239/wjd.v12.i8.1267
Decabromodiphenyl ether causes insulin resistance and glucose and lipid metabolism disorders in mice
Ayiguli Alimu, Haiqiemuhan Abudureman, Yong-Zhi Wang, Mei-Yan Li, Jia-Sui Wang, Zao-Ling Liu
Ayiguli Alimu, Haiqiemuhan Abudureman, Mei-Yan Li, Jia-Sui Wang, Zao-Ling Liu, Department of Epidemiology and Health Statistics, School of Public Health, Xinjiang Medical University, Urumqi 0991, Xinjiang Uygur Autonomous Region, China
Yong-Zhi Wang, Department of Public Health, Xinjiang Second Medical College, Cremayi 834000, Xinjiang Uygur Autonomous Region, China
Author contributions: Liu ZL participated in research design; Alimu A, Abudureman H, Wang ZW, Li MY, and Wang JS conducted the experiments; Alimu A and Liu ZL performed data analysis; Alimu A and Liu ZL wrote or edited the manuscript.
Supported by National Natural Science Foundation of China, No. 81760596; and Natural Science Foundation of Xinjiang Uygur Autonomous Region, No. 2019D01C209.
Institutional review board statement: Our research protocol was evaluated and approved by the Ethics Review Committee of the First Affiliated Hospital of Xinjiang Medical University (No. 20170214-107).
Institutional animal care and use committee statement: The animals were handled in accordance with the Guide for the Care and Use of Laboratory Animals.
Conflict-of-interest statement: No conflict of interest exits in the submission of this manuscript, and the manuscript has been approved by all authors for publication.
Data sharing statement: No other data available.
ARRIVE guidelines statement: I has read the "ARRIVE Guidelines" and has compiled and revised the manuscript according to the "ARRIVE Guidelines".
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zao-Ling Liu, PhD, Professor, Department of Epidemiology and Health Statistics, School of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Xinshi District, Urumqi 0991, Xinjiang Uygur Autonomous Region, China. 136497460@qq.com
Received: December 18, 2020
Peer-review started: December 18, 2020
First decision: May 3, 2021
Revised: May 15, 2021
Accepted: June 25, 2021
Article in press: June 25, 2021
Published online: August 15, 2021
Processing time: 233 Days and 5.2 Hours
Abstract
BACKGROUND

Decabromodiphenyl ether (BDE-209) is the most commonly used brominated flame retardant. Recently, BDE-209 has been suspected of being an environmental risk factor for metabolic diseases such as obesity, insulin resistance (IR), type 2 diabetes mellitus, and hypertension.

AIM

To investigate the effects of BDE-209 on IR and glucose and lipid metabolism in C57BL/6 mice.

METHODS

Adult male C57BL/6 mice were randomly divided into high, medium-high, medium, medium-low, and low dose BDE-209 groups, and a control group (n = 6 per group), which received 1000, 800, 600, 450, 300, and 0 mg/kg BDE-209, respectively. After BDE-209 exposure for 60 d, the mice were fasted overnight, and then sacrificed to obtain tissues. An automatic biochemical analyzer was used to detect serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C); enzyme-linked immunosorbent assay kits were used to detect fasting serum insulin (FINS), leptin (LEP), and adiponectin (Adp) levels; a blood glucose meter was used to detect fasting blood glucose (FBG). Morphological changes of the liver were observed by hematoxylin and eosin staining. Real-time quantitative polymerase chain reaction and Western blot were used to determine the messenger ribonucleic acid (mRNA) and protein levels, respectively, of LEP, Adp, and peroxisome proliferators activated receptor-γ (PPARγ) in mouse liver and adipose tissues.

RESULTS

There was a statistically significant difference in the weight of mice in each group after 45 and 60 d of exposure (P < 0.05). After 60 d of exposure, the weight of liver and adipose tissues in the exposure groups were greater than that of the control group (P < 0.05). The liver tissue structure was disordered and the liver tissues were accompanied by local inflammatory cell infiltration in the high, medium-high, and medium dose BDE-209 groups. The levels of FINS, insulin sensitivity index, Adp, and HDL-C were decreased in the BDE-209 group compared with the control group, as were the mRNA and protein levels of Adp in liver and adipose tissues (P < 0.05). Serum level of FBG and LEP were higher in the BDE-209 group than in controls. TC, TG, and LDL-C levels as well as the mRNA and protein expression of LEP and PPARγ in liver and adipose tissues were higher than those in the control group (P < 0.05). Homeostatic assessment model of IR was higher in the medium and medium-low dose BDE-209 groups (P < 0.05).

CONCLUSION

BDE-209 increases the body weight, fat and liver tissue weight, TC, TG, and LDL-C, reduces HDL-C, and causes IR in mice, which may be related to activating the PPARγ receptor.

Keywords: Decabromodiphenyl ether; Adipokine; Glucose and lipid metabolism; Protein expression; mRNA expression; Insulin resistance

Core Tip: Decabromodiphenyl ether (BDE-209) may be an environmental risk factor leading to obesity. There are limited literature reports on the correlation between BDE-209 and obesity. This type of research began with animal experiments, and the results showed that BDE-209 affects animal body weight, but the direction of the effect is not consistent. This study found that BDE-209 increased the body weight and body fat and liver tissue weight in mice, which may be related to the activation of peroxisome proliferators activated receptor-γ receptor and the abnormal differentiation of adipocytes. In obese patients, proinflammatory cytokines and interleukin-6 can cause insulin resistance through a variety of mechanisms.