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Race-specific associations of urinary phenols and parabens with adipokines in midlife women: The Study of Women's Health Across the Nation (SWAN)
2022
Lee, Seulbi | Karvonen-Gutierrez, Carrie | Mukherjee, Bhramar | Herman, William H. | Park, Sung Kyun
Adipokines, cytokines secreted by adipose tissue, may contribute to obesity-related metabolic disease. The role of environmental phenols and parabens in racial difference in metabolic disease burden has been suggested, but there is limited evidence. We examined the cross-sectional associations of urinary phenols and parabens with adipokines and effect modification by race. Urinary concentrations of 6 phenols (bisphenol-A, bisphenol-F, 2,4-diclorophenol, 2,5-diclorophenol, triclosan, benzophenone-3) and 4 parabens (methyl-paraben, ethyl-paraben, propyl-paraben, butyl-paraben) were measured in 2002–2003 among 1200 women (mean age = 52.6) enrolled in the Study of Women's Health Across the Nation Multi-Pollutant Study. Serum adipokines included adiponectin, high molecular weight (HMW)-adiponectin, leptin, soluble leptin receptor (sOB-R). Linear regression models were used to estimate the adjusted percentage change in adipokines per inter-quantile range (IQR) increase in standardized and log-transformed levels of individual urinary phenols and parabens. Bayesian kernel machine regression (BKMR) was used to evaluate the joint effect of urinary phenols and parabens as mixtures. Participants included white (52.5%), black (19.3%), and Asian (28.1%) women. Urinary 2,4-dichlorophenol was associated with 6.02% (95% CI: 1.20%, 10.83%) higher HMW-adiponectin and urinary bisphenol-F was associated with 2.60% (0.48%, 4.71%) higher sOB-R. Urinary methyl-paraben was associated with lower leptin in all women but this association differed by race: 8.58% (−13.99%, −3.18%) lower leptin in white women but 11.68% (3.52%, 19.84%) higher leptin in black women (P interaction = 0.001). No significant associations were observed in Asian women. Additionally, we observed a significant positive overall effect of urinary phenols and parabens mixtures in relation to leptin levels in black, but not in white or Asian women. Urinary bisphenol-F, 2,4-dichlorophenol and methyl-paraben may be associated with favorable profiles of adipokines, but methyl-paraben, widely used in hair and personal care products, was associated with unfavorable leptin levels in black women. Future studies are needed to confirm this racial difference.
Показать больше [+] Меньше [-]GCN5-mediated PKM2 acetylation participates in benzene-induced hematotoxicity through regulating glycolysis and inflammation via p-Stat3/IL17A axis
2022
Zhang, Wei | Guo, Xiaoli | Ren, Jing | Chen, Yujiao | Wang, Jingyu | Gao, Ai
Benzene is a common environmental carcinogen that induces leukemia. Studies suggest that metabolic disorder has a relationship with the toxicity of benzene. Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. However, the upstream and downstream regulatory mechanisms of PKM2 in benzene-induced hematotoxicity and the therapeutic effects of targeting PKM2 in vivo are unclear. This study aims to provide insights into the new mechanism of benzene-induced hematotoxicity and reveal the therapeutic significance of targeting PKM2. Herein, we demonstrated that PKM2-dependent glycolysis contributes to benzene-induced hematotoxicity by regulating inflammation reaction. Mechanistically, acetylated proteomics revealed that 1,4-benzoquinone (1,4-BQ) induced acetylation of PKM2 at position K66, and this modification contributed to the increase of PKM2 expression and can be inhibited by inhibition of acetyltransferase GCN5. Meanwhile, the elevated PKM2 was shown to prompt the activation of nuclear phosphorylated Stat3 (p-Stat3) and IL17A. Clinically, pharmacological inhibition of PKM2 alleviated the blood toxicity induced by benzene, which was mainly characterized by an increase in routine blood parameters and improvement of hematopoietic imbalance. Besides, elevated PKM2 is a promising biomarker in people occupationally exposed to benzene. Overall, we identified PKM2/p-Stat3/IL-17A axis participates in the hematotoxicity of benzene, and targeting PKM2 has certain therapeutic implications in hematologic diseases.
Показать больше [+] Меньше [-]Effect of polystyrene nanoplastics on cell apoptosis, glucose metabolism, and antibacterial immunity of Eriocheir sinensis
2022
Nan, Xingyu | Jin, Xingkun | Song, Yu | Zhou, Kaimin | Qin, Yukai | Wang, Qun | Li, Weiwei
The adverse effects of plastic waste and nanoplastics on the water environment have become a focus of global attention in recent years. In the present study, using adult Chinese mitten crabs (Eriocheir sinensis) as an animal model, the bioaccumulation and the in vivo and in vitro toxicity of polystyrene nanoplastics (PS NPs), alone or in combination with the bacteria, were investigated. This study aimed to investigate the effects of PS NPs on apoptosis and glucose metabolism in Chinese mitten crabs, and whether PS NPs could synergistically affect the antibacterial immunity of crabs. We observed that NPs were endocytosed by hemocytes, which are immune cells in crustaceans and are involved in innate immunity. The RNA sequencing data showed that after hemocytes endocytosed NPs, apoptosis and glucose metabolism-related gene expression was significantly induced, resulting in abnormal cell apoptosis and a glucose metabolism disorder. In addition, exposure to NPs resulted in changes in the antimicrobial immunity of crabs, including changes in antimicrobial peptide expression, survival, and bacterial clearance. In summary, NPs could be endocytosed by crab hemocytes, which adversely affected the cell apoptosis, glucose metabolism, and antibacterial immunity of Eriocheir sinensis. This study revealed the effects of NPs on crab immunity and lays the foundation for further exploration of the synergistic effect of NPs and bacteria.
Показать больше [+] Меньше [-]The effect of toxic components on metabolomic response of male SD rats exposed to fine particulate matter
2021
Geng, Ningbo | Song, Xiaoyao | Cao, Rong | Luo, Yun | A, Mila | Cai, Zhengang | Yu, Kejie | Gao, Yuan | Ni, Yuwen | Zhang, Haijun | Chen, Jiping
PM₂.₅ pollution was associated with numerous adverse health effects. However, PM₂.₅ induced toxic effects and the relationships with toxic components remain largely unknown. To evaluate the metabolic toxicity of PM₂.₅ at environmentally relevant doses, investigate the seasonal variation of PM₂.₅ induced toxicity and the relationship with toxic components, a combination of general pathophysiological tests and metabolomics analysis was conducted in this study to explore the response of SD rats to PM₂.₅ exposure. The result of general toxicology analysis revealed unconspicuous toxicity of PM₂.₅ under environmental dose, but winter PM₂.₅ at high dose caused severe histopathological damage to lung. Metabolomic analysis highlighted significant metabolic disorder induced by PM₂.₅ even at environmentally relevant doses. Lipid metabolism and GSH metabolism were primarily influenced by PM₂.₅ exposure due to the high levels of heavy metals. In addition, high levels of organic compounds such as PAHs, PCBs and PCDD/Fs in winter PM₂.₅ bring multiple overlaps on the toxic pathways, resulting in larger pulmonary toxicity and metabolic toxicity in rats than summer.
Показать больше [+] Меньше [-]Nitrate exposure induces intestinal microbiota dysbiosis and metabolism disorder in Bufo gargarizans tadpoles
2020
Xie, Lei | Zhang, Yuhui | Gao, Jinshu | Li, Xinyi | Wang, Hongyuan
Excess nitrate has been reported to be associated with many adverse effects in humans and experimental animals. However, there is a paucity of information of the effects of nitrate on intestinal microbial community. In this study, the effects of nitrate on development, intestinal microbial community, and metabolites of Bufo gargarizans tadpoles were investigated. B. gargarizans were exposed to control, 5, 20 and 100 mg/L nitrate-nitrogen (NO₃–N) from eggs to Gosner stage 38. Our data showed that the body size of tadpoles significantly decreased in the 20 and 100 mg/L NO₃–N treatment group when compared to control tadpoles. Exposure to 20 and 100 mg/L NO₃–N also caused indistinct cell boundaries and nuclear pyknosis of mucosal epithelial cells in intestine of tadpoles. In addition, exposure to NO₃–N significantly altered the intestinal microbiota diversity and structure. The facultative anaerobic Proteobacteria occupy the niche of the obligately anaerobic Bacteroidetes and Fusobacteria under the pressure of NO₃–N exposure. According to the results of functional prediction, NO₃–N exposure affected the fatty acid metabolism pathway and amino acid metabolism pathway. The whole-body fatty acid components were found to be changed after exposure to 100 mg/L NO₃–N. Therefore, we concluded that exposure to 20 and 100 mg/L NO₃–N could induce deficient nutrient absorption in intestine, resulting in malnutrition of B. gargarizans tadpoles. High levels of NO₃–N could also change the intestinal microbial communities, causing dysregulation of fatty acid metabolism and amino acid metabolism in B. gargarizans tadpoles.
Показать больше [+] Меньше [-]Gastrointestinal dysbiosis following diethylhexyl phthalate exposure in zebrafish (Danio rerio): Altered microbial diversity, functionality, and network connectivity
2020
Buerger, Amanda N. | Dillon, David T. | Schmidt, Jordan | Yang, Tao | Zubcevic, Jasenka | Martyniuk, Christopher J. | Bisesi, Joseph H.
Microbiome community structure is intimately involved in key biological functions in the gastrointestinal (GI) system including nutrient absorption and lipid metabolism. Recent evidence suggests that disruption of the GI microbiome is a contributing factor to metabolic disorders and obesity. Poor diet and chemical exposure have been independently shown to cause disruption of the GI microbiome community structure and function. We hypothesized that the addition a chemical exposure to overfeeding exacerbates adverse effects on the GI microbiome community structure and function. To test this hypothesis, adult zebrafish were fed a normal feeding regime (Control), an overfeeding regime (OF), or an overfeeding regime contaminated with diethylhexyl phthalate (OF + DEHP), a suspected obesogen-inducing chemical. After 60 days, fecal matter was collected for sequencing, identification, and quantification of the GI microbiome using the 16s rRNA hypervariable region. Analysis of beta diversity indicated distinct microbial profiles between treatments with the largest divergence between Control and OF + DEHP groups. Based upon functional predictions, OF + DEHP treatment altered carbohydrate metabolism, while both OF and OF + DEHP affected biosynthesis of fatty acids and lipid metabolism. Co-occurrence network analysis revealed decreases in cluster size and a fracturing of the microbial community network into unconnected components and a loss of keystone species in the OF + DEHP treatment when compared to Control and OF treatments. Data suggest that the addition of DEHP in the diet may exacerbate microbial dysbiosis, a consequence that may explain in part its role as an obesogenic chemical.
Показать больше [+] Меньше [-]Stereoselective effects of ibuprofen in adult zebrafish (Danio rerio) using UPLC-TOF/MS-based metabolomics
2018
Song, Yue | Chai, Tingting | Yin, Zhiqiang | Zhang, Xining | Zhang, Wei | Qian, Yong-Zhong | Qiu, Jing
Ibuprofen (IBU), as a commonly used non-steroidal anti-inflammatory drug (NSAID) and pharmaceutical and personal care product (PPCP), is frequently prescribed by doctors to relieve pain. It is widely released into environmental water and soil in the form of chiral enantiomers by the urination and defecation of humans or animals and by sewage discharge from wastewater treatment plants. This study focused on the alteration of metabolism in the adult zebrafish (Danio rerio) brain after exposure to R-(-)-/S-(+)-/rac-IBU at 5 μg L−1 for 28 days. A total of 45 potential biomarkers and related pathways, including amino acids and their derivatives, purine and its derivatives, nucleotides and other metabolites, were observed with untargeted metabolomics. To validate the metabolic disorders induced by IBU, 22 amino acids and 3 antioxidant enzymes were selected to be quantitated and determined using targeted metabolomics and enzyme assay. Stereoselective changes were observed in the 45 identified biomarkers from the untargeted metabolomics analysis. The 22 amino acids quantitated in targeted metabolomics and 3 antioxidant enzymes determined in enzyme assay also showed stereoselective changes after R-(-)-/S-(+)-/rac-IBU exposure. Results showed that even at a low concentration of R-(-)-/S-(+)-/rac-IBU, disorders in metabolism and antioxidant defense systems were still induced with stereoselectivity. Our study may enable a better understanding of the risks of chiral PPCPs in aquatic organisms in the environment.
Показать больше [+] Меньше [-]Exposure to the fungicide propamocarb causes gut microbiota dysbiosis and metabolic disorder in mice
2018
Wu, Sisheng | Jin, Cuiyuan | Wang, Yueyi | Fu, Zhengwei | Jin, Yuanxiang
Propamocarb (PM) is a widely used fungicide with property of affecting fatty acid and phospholipid biosynthesis in funguses. In this study, we explored its effects on mice gut microbiota and metabolism by exposing mice to 3, 30, and 300 mg/L PM through drinking water for a duration of 28 days. We observed that the transcription of hepatic genes related to regulate lipid metabolism were perturbed by PM exposure. The microbiota in the cecal contents and feces changed during or after PM exposure at phylum or genus levels. 16S rRNA gene sequencing for the cecal content revealed shifted in overall microbial structure after PM exposure, and operational taxonomic unit (OTU) analysis indicated that 32.2% of OTUs changed by 300 mg/mL PM exposure for 28 days. In addition, based on 1H NMR analysis,a total of 20 fecal metabolites mainly including succinate, short chain fatty acids, bile acids and trimethylamine were found to be significantly influenced by exposure to 300 mg/L PM.,. These metabolites were tightly correlated to host metabolism. Our findings indicated that high doses of PM exposure could disturb mice metabolism through, or partly through, altering the gut microbiota and microbial metabolites.
Показать больше [+] Меньше [-]PCBs–high-fat diet interactions as mediators of gut microbiota dysbiosis and abdominal fat accumulation in female mice
2018
Chi, Yulang | Lin, Yi | Zhu, Huimin | Huang, Qiansheng | Ye, Guozhu | Dong, Sijun
Polychlorinated biphenyls (PCBs), one type of lipophilic pollutant, are ubiquitous in daily life. PCBs exposure has been implicated in the alterations of gut microbial community which is profoundly associated with diverse metabolic disorders, including obesity. High-fat diet (H) is a dietary pattern characterized by a high percentage of fat. According to the theory that similarities can be easily solvable in each other, PCBs and H exposures are inevitably and objectively coexistent in a real living environment, prompting great concerns about their individual and combined effects on hosts. However, the effects of PCBs-H interactions on gut microbiota and obesity are still incompletely understood. In the present study, the effects of PCBs and/or H on the gut microbiota alteration and obesity risk in mice were examined and the interactions between PCBs and H were investigated. Obtained results showed that PCBs and/or H exposure induced prominent variations in the gut microbiota composition and diversity. Exposure to PCBs also resulted in higher body fat percentage, greater size of abdominal subcutaneous adipocytes and increased expression of proinflammatory cytokines including TNF-α, iNOS and IL-6. Such PCBs-induced changes could be further enhanced upon the co-exposure of H, implying that obese individuals may be vulnerable to PCBs exposure. Taken together, the present study is helpful for a better understanding of the gut microbiota variation influenced by PCBs and/or H exposure, and furthermore, provides a novel insight into the mechanism of PCBs-H interactions on host adiposity.
Показать больше [+] Меньше [-]Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice
2017
Liu, Qian | Shao, Wentao | Zhang, Chunlan | Xu, Cheng | Wang, Qihan | Liu, Hui | Sun, Haidong | Jiang, Zhaoyan | Gu, Aihua
Organochlorine pesticides (OCPs) can persistently accumulate in body and threaten human health. Bile acids and intestinal microbial metabolism have emerged as important signaling molecules in the host. However, knowledge on which intestinal microbiota and bile acids are modified by OCPs remains unclear. In this study, adult male C57BL/6 mice were exposed to p, p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH) for 8 weeks. The relative abundance and composition of various bacterial species were analyzed by 16S rRNA gene sequencing. Bile acid composition was analyzed by metabolomic analysis using UPLC-MS. The expression of genes involved in hepatic and enteric bile acids metabolism was measured by real-time PCR. Expression of genes in bile acids synthesis and transportation were measured in HepG2 cells incubated with p, p’-DDE and β-HCH. Our findings showed OCPs changed relative abundance and composition of intestinal microbiota, especially in enhanced Lactobacillus with bile salt hydrolase (BSH) activity. OCPs affected bile acid composition, enhanced hydrophobicity, decreased expression of genes on bile acid reabsorption in the terminal ileum and compensatory increased expression of genes on synthesis of bile acids in the liver. We demonstrated that chronic exposure of OCPs could impair intestinal microbiota; as a result, hepatic and enteric bile acid profiles and metabolism were influenced. The findings in this study draw our attention to the hazards of chronic OCPs exposure in modulating bile acid metabolism that might cause metabolic disorders and their potential to cause related diseases in human.
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