Mediating Effects of Insulin Resistance on Lipid Metabolism with Elevated Paraben Exposure in the General Taiwan Population

Po-Chin Huang ¹ Hsin-Chang Chen ² Han-Bin Huang ³ Yu-Jung Lin ¹ Wan-Ting Chang ¹ Shih-Hao Leung ⁴ Hsi Chen ⁴ Jung-Wei Chang ^5*

• ¹ National Institute of Environmental Medicine, National Health Research Institutes (Taiwan), Zhunan, Miaoli County, Taiwan
• ² Department of Chemistry, Tunghai University, Taichung, Taiwan
• ³ School of Public Health, National Defense Medical Center, Taipei, Taiwan
• ⁴ Institute of Environmental and Occupational Health Sciences, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
• ⁵ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

Parabens are commonly used to prevent bacteria from growing in cosmetics and foodstuffs. Parabens have been reported to influence hormone regulation, potentially leading to metabolic anomalies, including insulin resistance and obesity. However, there is a paucity of knowledge regarding the relationship between urinary paraben levels and lipid metabolism in the general Taiwanese population. Therefore, the objective of this study was to determine whether the mediating role of insulin resistance exists between paraben exposure and lipid metabolism. We selected the data of 264 adult participants from a representative survey in five major Taiwan area in 2013. UPLC tandem mass spectrometry was used to examine four urine parabens: methyl- (MeP), ethyl- (EtP), propyl- (PrP) and butyl- (BuP). Blood samples were analyzed for concentrations of glucose and lipid metabolic indices using the DxI 800 immunoassay analyzer and immunoradiometric assay kit. The relationship between urinary paraben levels and metabolism indices were evaluated through a multiple linear regression analysis. Finally, a mediation analysis was employed to understand the underlying mechanism by which paraben exposure influences lipid metabolism through insulin resistance. The significant positive association between MeP exposure and Castelli risk index I (CRI-I; Beta= 0.05, p= 0.049) was found, and also exhibited the similar associations between EtP exposure and low-density lipoprotein cholesterol (Beta= 0.10, p= 0.001), total cholesterol (Beta= 0.06, p= 0.003), and non-HDL cholesterol (NHC; Beta= 0.08, p= 0.005). EtP exhibited a significant positive association with triglyceride BMI (TyG-BMI; Beta= 0.02, p= 0.040). Additionally, TyG-BMI was positively associated with CRI-I (Beta= 0.98, p< 0.001), CRI-II (Beta= 1.03, p< 0.001) and NHC (Beta= 0.63, p< 0.001). Moreover, insulin resistance served as mediators for the effects of EtP exposure on lipid metabolism indices. The results indicate that changes in insulin resistance mediated the relationship between urinary paraben and lipid metabolism. Large-scale epidemiological and animal studies are warranted to identify biological mechanisms underlying validate these relationships.