Targeted Lipidomics Reveal the Effect of Perchlorate on Lipid Profiles in Liver of High-Fat Diet Mice

Abstract

Perchlorate, commonly available in drinking water and food, acts on the iodine uptake by the thyroid affecting lipid metabolism. High-fat diets leading to various health problems continually raise public concern. In the present study, liver lipid metabolism profiles and metabolic pathways were investigated in C57BL/6J mice chronically exposed to perchlorate using targeted metabolomics. Mice were fed a high-fat diet and treated orally with perchlorate at 0.1 mg/kg bw (body weight), 1 mg/kg bw and 10 mg/kg bw daily for 12 weeks. Perchlorate induced disorders of lipid metabolism in vivo and hepatic lipid accumulation confirmed by serum biochemical parameters and histopathological examination. There were 34 kinds of lipid in liver detected by UHPLC-MS/MS and key metabolites were identified by multivariate statistical analysis evaluated with VIP > 1, p-value < 0.05, fold change > 1.2 or < 0.8. Perchlorate low, medium and high dose groups were identified with 11, 7 and 8 significantly altered lipid metabolites compared to the control group, respectively. The results of the metabolic pathway analysis revealed that the differential metabolites classified into different experimental groups contribute to the glycerophospholipid metabolic pathway. These findings provide insights into the effects of perchlorate on lipid metabolism during long-term exposure to high-fat diets and contribute to the evaluation of perchlorate liver toxic mechanisms and health effects.

The Hepatoprotective Effect of Leonurine Hydrochloride Against Alcoholic Liver Disease Based on Transcriptomic and Metabolomic Analysis

“…Raw data were processed as previously described ( 19 ). Specifically, the quantification of target lipid metabolites was based on signal intensity relative to the corresponding internal standard by the multiple reaction MRM of triple quadrupole mass spectrometry.…”

“…The collected lipid metabolites of the cell samples (at least four replicates per group) were analyzed using QTRAP 6500 LC-MS/MS system (AB Sciex, United States) equipped with Acquity HSS T3 column (2.1 mm × 100 mm i.d., 1.8 μm, Waters, United States) as previously described ( 19 ). Specifically, the mobile phase solvent A: water/methanol/acetonitrile (1/1/1, v/v/v) containing 10 mM ammonium formate and 0.05% formic acid; solvent B: isopropanol.…”

“…The conditions used for the electrospray source were previously described ( 19 ). Specifically, the ion source temperature, 450°C; the ion spray voltage, 5,500 V in positive mode (5,500 V in negative model); the ion source gas I, 55 psi; the gas II, 60 psi; the curtain gas, 30 psi; the collision gas, medium; quantification of ion pairs corresponding to lipids by multiple reaction monitoring mode (MRM); detection widow, 60 s. According to our previous study, mass spectrometry information of the target lipid metabolites was prepared ( 19 ). Specifically, quality control (QC) sample was prepared by mixing equal amounts (50 μL) of each extracted sample.…”

Trends in the Exposure, Distribution, and Health Risk Assessment of Perchlorate among Crayfish in the Middle and Lower Reaches of the Yangtze River

“…Thus, perchlorate can compete with iodide ions for binding to the NIS, which results in interruption of the production of triiodothyronine (T3) and thyroxine (T4) and then causes hypothyroidism [ 6 , 7 ]. In addition, perchlorate can also cause disorders of lipid metabolism in mice [ 8 ]. The adverse effects of perchlorate mainly occur in people with thyroid disorders—especially pregnant women and infants [ 9 ].…”

Associations of thiocyanate, nitrate, and perchlorate exposure with dyslipidemia: a cross-sectional, population-based analysis

“…Nevertheless, further research is required to investigate the pathways between thiocyanate exposure and dyslipidemia.Our analysis also revealed that urinary perchlorate was negatively associated with elevated LDL-C, but not other dyslipidemia indicators, which is interesting and somewhat unexpected. This is because in a recent animal experiment, mice fed a high-fat diet and exposed to perchlorate exhibited no signi cant changes in LDL-C, though HDL-C was signi cantly increased(Wang et al 2022c). Additionally, a study of zebra sh found that perchlorate exposure (relative to control treatment) failed to alter liver or systemic lipid accumulation(Minicozzi et al 2021).…”