Decabromodiphenyl ether disturbs hepatic glycolipid metabolism by regulating the PI3K/AKT/GLUT4 and mTOR/PPARγ/RXRα pathway in mice and L02 cells

Zhu, Yupeng; Li, Jing; Li, Xiangyang; Zheng, Dan; Zhou, Guang‐Peng; Zhang, Yue; Sang, Yujian; Shi, Zhixiong; Sun, Zhiwei; Zhou, Xianqing

doi:10.1016/j.scitotenv.2020.142936

Cited by 28 publications

(16 citation statements)

References 54 publications

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“…Once activated, Akt phosphorylates its downstream glycogen synthase kinase 3β (GSK-3β) to increase glycogen synthesis and maintains lipid homeostasis [ 38 ]. Moreover, the insulin-stimulated phosphorylation of Akt is crucial to insulin-responsive GLUT, which is from cytosol to the cell membrane to facilitate glucose transport into cells [ 39 ]. Among the GLUT subtypes, GLUT4 is mainly enriched in the liver, pancreas, and skeletal muscle [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway

Chen

et al. 2022

Antioxidants

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Type 2 diabetes mellitus (T2DM) is a multisystem and complex metabolic disorder which is associated with insulin resistance and impairments of pancreatic β-cells. Previous studies have shown that icariside II (ICS II), one of the main active ingredients of Herba Epimedii, exerts potent anti-inflammatory and anti-oxidative properties. In this study, we investigated whether ICS II exerted anti-T2DM profile and further explored its possible underlying mechanism both in vivo and in vitro. db/db mice were administered ICS II (10, 20, 40 mg·kg−1) for 7 weeks. We found that ICS II dose-dependently attenuated hyperglycemia and dyslipidemia, as well as inhibited hepatic steatosis and islet architecture damage in db/db mice. Moreover, ICS II not only dramatically reduced inflammatory cytokines and oxidative stress, but also up-regulated PPARα/γ protein expressions, phosphorylation of Akt, GSK3β and IR, meanwhile, down-regulated phosphorylation of NF-κB(p65) and IRS1 in db/db mice. In palmitic acid (PA)-treated HepG2 or MIN6 cells, ICS II (5−20 μM) concentration-dependently promoted the cell viability via mediating PPARα/γ/NF-κB signaling pathway. PPARα/γ knockout by CRISPR-Cas9 system partly abolished the protective effects of ICS II on HepG2 or MIN6 cells following PA insults. These findings reveal that ICS II effectively confer anti-T2DM property by targeting PPARα/γ through mediation of ROS/NF-κB/IRS1 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway

Chen

et al. 2022

Antioxidants

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“…In rats exposed to 14 mg/kg BW/day of a mix of PBDE congeners, a decrease in insulin-stimulated glucose oxidation and an increase in isoproterenol-stimulated lipolysis was observed in adipocytes [97]. A significant disruption of the metabolism of lipids and carbohydrates was also observed in mice exposed to high doses of BDE-209 [87,91].…”

Section: Metabolic Disruptionmentioning

confidence: 95%

“…Metabolites of BDE-47 (3-MeO-BDE47, 3-MeO-BDE47, 5-MeO-BDE47, 5-OH-BDE47) increased the activity of superoxide dismutase (SOD), decreased the levels of glutathione (GSH), and increased ROS in LO2 cells in a dose-dependent manner [86]. In another study, exposure of LO2 cells to 10 and 50 µM BDE-209 also led to a significant increase in ROS levels [87]. The treatment of HS-68 human cell culture to 50 µmol/L BDE-47, 100 µmol/L BDE-99, 2 µmol/L BDE-209 led to an increase in the levels of intracellular ROS [85].…”

Section: Induction Of Oxidative Stressmentioning

confidence: 97%

“…A recent study from another research group reported activation of PI3K/Akt signaling, which is an upstream activator of mTOR, by BDE-47 and BDE-85 in pancreatic beta-cells [185]. mTOR was also activated in human-derived hepatic cells (HepaRG) by 25 µM of BDE-47 or BDE-99 [186] and in the human fetal hepatocyte line (LO2) by 50 µM of BDE-209 [87]. Conversely, treatment of human preadipocytes with 1 or 3 µM of BDE-28 resulted in decreased phosphorylation (activity) of several key players in the mTOR pathway [98].…”

Section: Insulin-like Growth Factor (Igf) and Mechanistic Target Of R...mentioning

confidence: 99%

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Mechanisms of Male Reproductive Toxicity of Polybrominated Diphenyl Ethers

Arowolo¹,

Pilsner²,

Sergeyev³

et al. 2022

Preprint

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Polybrominated diphenyl ethers (PBDE) are a group of flame retardants used in a variety of artificial materials. Despite phasing out in most industrial countries, they persist in the environment and human tissues due to their persistence, lipophilicity, and bioaccumulation. Populational and experimental studies demonstrate male reproductive toxicity of PBDEs including increased incidence of genital malformations (hypospadias and cryptorchidism), altered weight of testes and other reproductive tissues, altered testes histology and transcriptome, decreased sperm production and sperm quality, altered epigenetic regulation of developmental genes in spermatozoa and altered secretion of reproductive hormones. A broad range of mechanistic hypotheses of PBDE reproductive toxicity has been suggested. Among these hypotheses, oxidative stress, disruption of estrogenic signaling, and mitochondria disruption are affected by PBDE concentrations much higher, than concentrations found in human tissues, making them unlikely links between exposures and adverse reproductive outcomes in the general population. Robust evidence suggests that at environmentally relevant doses, PBDEs and their metabolites may affect male reproductive health via mechanisms including AR antagonism and the disruption of a complex network of metabolic signaling.

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“…It is reported that intestinal hypoxia-inducible factor 2α signaling is positively correlated with hepatic metabolic disorder ( 5 ), indicating the tight link between gut-liver axis and glycolipid metabolism homeostasis. Recent evidence has indicated that environmental pollutant, such as decabromodiphenyl ether, disrupts glycolipid metabolism through regulating the PI3K/AKT/GLUT4 pathway and the mTOR/PPARγ/RXRα pathway ( 6 ). Since people are accustomed to a sedentary and food-abundant lifestyle, glycolipid metabolism disorders have been highly globally prevalent, including non-alcoholic fatty liver disease (NAFLD) ( 7 ), insulin resistance ( 8 ), and diabetes ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Emerging Trends and Hot Spots in Hepatic Glycolipid Metabolism Research From 2002 to 2021: A Bibliometric Analysis

et al. 2022

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Glycolipid metabolic diseases, including type 2 diabetes, non-alcoholic fatty liver disease, obesity, hypertension, dyslipidemia, and atherosclerosis, which have become a major public health concern worldwide, are mainly triggered by hepatic glycolipid metabolism disorder. Bibliometric analysis has provided a comprehensive review of developments in hepatic glycolipid metabolism research and changes in research hotspots over the past 20 years. The articles regarding hepatic glycolipid metabolism from 2002 to 2021 were identified from the Science Citation Index-Expanded of Web of Science Core Collection. Acquired data were then processed by the CiteSpace software and the Online Analysis Platform of Literature Metrology to analyze trends and predict hot spots in this field. A total of 4,856 articles regarding hepatic glycolipid metabolism published from 2002 to 2021 were selected. The leading country was China. The Chinese Academy of Sciences was the most productive institution. Co-citation cluster labels revealed characteristics of ten main clusters: non-alcoholic fatty liver disease, gut microbiota, adiponectin, fructose, fgf21, fatty acid, liver x receptor, nr4a, obese mice, and bile acids. Keyword bursts analysis indicated that management, non-alcoholic fatty liver disease, and modulation were the newly emerging research hot spots. We described the overall structure of scientific research on hepatic glycolipid metabolism and presented systematic information to other researchers. The current focus on NAFLD and gut microbiota is critical to further study and will help explore effective therapeutic strategy for aberrant glycolipid metabolism in liver.

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Decabromodiphenyl ether disturbs hepatic glycolipid metabolism by regulating the PI3K/AKT/GLUT4 and mTOR/PPARγ/RXRα pathway in mice and L02 cells

Cited by 28 publications

References 54 publications

Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway

Icariside II Exerts Anti-Type 2 Diabetic Effect by Targeting PPARα/γ: Involvement of ROS/NF-κB/IRS1 Signaling Pathway

Mechanisms of Male Reproductive Toxicity of Polybrominated Diphenyl Ethers

Emerging Trends and Hot Spots in Hepatic Glycolipid Metabolism Research From 2002 to 2021: A Bibliometric Analysis

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