Methylation Partially Mediated the Association of Exposure to Triclosan but Not Triclocarban with Type 2 Diabetes Mellitus: A Case-Control Study

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Nov 27

PMID 39596180

Authors

Qian Gao

Changsheng Huan

Zexin Jia

Qingqing Cao

Pengcheng Yuan

Xin Li

Chongjian Wang

Zhenxing Mao

Wenqian Huo

Affiliations

Soon will be listed here.

Abstract

This study aimed to evaluate the association of TCs (triclosan (TCS) and triclocarban) exposure with T2DM and glucose metabolism-related indicators and the mediating effect of methylation on their associations. A total of 956 participants (330 T2DM and 626 controls) were included in this case-control study. Logistic regression and generalized linear models were used to assess the effect of TCs on T2DM and glucose metabolism-related indicators. The dose-response relationship between TCs and T2DM was analyzed by restricted cubic spline. Finally, after evaluating the association between TCs and methylation levels, the mediating effect of methylation on the TC-associated T2DM was estimated. Each 1-unit increase in TCS levels was associated with a 13.2% increase in the risk of T2DM (OR = 1.132, 95% CI: 1.062, 1.207). A linear dose-response relationship was found between TCS and T2DM. TCS was negatively associated with methylation. Moreover, mediation analysis revealed that methylation mediated 14.54% of the relationship between TCS exposure and T2DM. Exposure to TCS was associated with a higher prevalence of T2DM. methylation partially mediated the association of TCS with T2DM. Our findings may provide new insights into the treatment of T2DM, and the study of the biological mechanisms of T2DM.

References

Dai Y, Chen W, Qi H, Liu Q . Effect of bisphenol A on SOCS-3 and insulin signaling transduction in 3T3-L1 adipocytes. Mol Med Rep. 2016; 14(1):331-6. DOI: 10.3892/mmr.2016.5224. View

Hou Y, Li S, Xia L, Yang Q, Zhang L, Zhang X . Associations of urinary phenolic environmental estrogens exposure with blood glucose levels and gestational diabetes mellitus in Chinese pregnant women. Sci Total Environ. 2020; 754:142085. DOI: 10.1016/j.scitotenv.2020.142085. View

Fisher B, Frederiksen H, Andersson A, Juul A, Thankamony A, Ong K . Serum Phthalate and Triclosan Levels Have Opposing Associations With Risk Factors for Gestational Diabetes Mellitus. Front Endocrinol (Lausanne). 2018; 9:99. PMC: 5859030. DOI: 10.3389/fendo.2018.00099. View

Ma H, Zheng L, Li Y, Pan S, Hu J, Yu Z . Triclosan reduces the levels of global DNA methylation in HepG2 cells. Chemosphere. 2012; 90(3):1023-9. DOI: 10.1016/j.chemosphere.2012.07.063. View

Du G, Yu M, Wang L, Hu W, Song L, Lu C . Transcriptome and DNA Methylome Dynamics during Triclosan-Induced Cardiomyocyte Differentiation Toxicity. Stem Cells Int. 2018; 2018:8608327. PMC: 6231387. DOI: 10.1155/2018/8608327. View

Barros R, Gustafsson J . Estrogen receptors and the metabolic network. Cell Metab. 2011; 14(3):289-99. DOI: 10.1016/j.cmet.2011.08.005. View

Wei D, Shi J, Xu H, Guo Y, Wu X, Chen Z . Prospective study on the joint effect of persistent organic pollutants and glucose metabolism on chronic kidney disease: Modifying effects of lifestyle interventions. Sci Total Environ. 2024; 951:175694. DOI: 10.1016/j.scitotenv.2024.175694. View

Niwa Y, Kanda H, Shikauchi Y, Saiura A, Matsubara K, Kitagawa T . Methylation silencing of SOCS-3 promotes cell growth and migration by enhancing JAK/STAT and FAK signalings in human hepatocellular carcinoma. Oncogene. 2005; 24(42):6406-17. DOI: 10.1038/sj.onc.1208788. View

Ward J, Casagrande S, Cowie C . Urinary phenols and parabens and diabetes among US adults, NHANES 2005-2014. Nutr Metab Cardiovasc Dis. 2020; 30(5):768-776. PMC: 8772274. DOI: 10.1016/j.numecd.2020.01.005. View

10.

Lee S, Karvonen-Gutierrez C, Mukherjee B, Herman W, Harlow S, Park S . Urinary concentrations of phenols and parabens and incident diabetes in midlife women: The Study of Women's Health Across the Nation. Environ Epidemiol. 2021; 5(5):e171. PMC: 8683147. DOI: 10.1097/EE9.0000000000000171. View

11.

Liu Z, Lu Y, Zhong K, Wang C, Xu X . The associations between endocrine disrupting chemicals and markers of inflammation and immune responses: A systematic review and meta-analysis. Ecotoxicol Environ Saf. 2022; 234:113382. DOI: 10.1016/j.ecoenv.2022.113382. View

12.

Stumvoll M, Goldstein B, van Haeften T . Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005; 365(9467):1333-46. DOI: 10.1016/S0140-6736(05)61032-X. View

13.

Ouyang F, Tang N, Zhang H, Wang X, Zhao S, Wang W . Maternal urinary triclosan level, gestational diabetes mellitus and birth weight in Chinese women. Sci Total Environ. 2018; 626:451-457. PMC: 5849787. DOI: 10.1016/j.scitotenv.2018.01.102. View

14.

Qi H, Dai Y, Chen W, Liu Q . SOCS-3 contributes to bisphenol a exposure-induced insulin resistance in hepatocytes. Sci China Life Sci. 2019; 62(12):1597-1600. DOI: 10.1007/s11427-018-1560-2. View

15.

Bluyssen H, Rastmanesh M, Tilburgs C, Jie K, Wesseling S, Goumans M . IFN gamma-dependent SOCS3 expression inhibits IL-6-induced STAT3 phosphorylation and differentially affects IL-6 mediated transcriptional responses in endothelial cells. Am J Physiol Cell Physiol. 2010; 299(2):C354-62. DOI: 10.1152/ajpcell.00513.2009. View

16.

Zhang Y, Lin C, Chen R, Luo L, Huang J, Liu H . Association analysis of SOCS3, JAK2 and STAT3 gene polymorphisms and genetic susceptibility to type 2 diabetes mellitus in Chinese population. Diabetol Metab Syndr. 2022; 14(1):4. PMC: 8734348. DOI: 10.1186/s13098-021-00774-w. View

17.

Pedroso J, Ramos-Lobo A, Donato Jr J . SOCS3 as a future target to treat metabolic disorders. Hormones (Athens). 2018; 18(2):127-136. DOI: 10.1007/s42000-018-0078-5. View

18.

Bedoux G, Roig B, Thomas O, Dupont V, Le Bot B . Occurrence and toxicity of antimicrobial triclosan and by-products in the environment. Environ Sci Pollut Res Int. 2011; 19(4):1044-65. DOI: 10.1007/s11356-011-0632-z. View

19.

Dodson R, Boronow K, Susmann H, Udesky J, Rodgers K, Weller D . Consumer behavior and exposure to parabens, bisphenols, triclosan, dichlorophenols, and benzophenone-3: Results from a crowdsourced biomonitoring study. Int J Hyg Environ Health. 2020; 230:113624. DOI: 10.1016/j.ijheh.2020.113624. View

20.

Shi M, Lin Z, Ye L, Chen X, Zhang W, Zhang Z . Estrogen receptor-regulated SOCS3 modulation via JAK2/STAT3 pathway is involved in BPF-induced M1 polarization of macrophages. Toxicology. 2020; 433-434:152404. DOI: 10.1016/j.tox.2020.152404. View