Germ-free status but not subacute polychlorinated biphenyl (PCB) exposure altered hepatic phosphatidylcholine and ether-phosphatidylcholine levels in mice.

Publisher: Elsevier Country of Publication: Ireland NLM ID: 0361055 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3185 (Electronic) Linking ISSN: 0300483X NLM ISO Abbreviation: Toxicology Subsets: MEDLINE

Publication: Limerick : Elsevier
Original Publication: Amsterdam. Elsevier/North-Holland.

Polychlorinated Biphenyls*/toxicity ; Liver*/metabolism ; Liver*/drug effects ; Phosphatidylcholines*/metabolism ; Germ-Free Life*; Animals ; Female ; Mice ; Mice, Inbred C57BL ; Gastrointestinal Microbiome/drug effects ; Lipidomics

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that pose a current ecosystem and human health concern. PCB exposure impacts the gut microbiome in animal models, suggesting a mechanistic link between PCB exposure and adverse health outcomes. The presence and absence of the microbiome and exposure to PCBs independently affect the lipid composition in the liver, which in turn affects the PCB disposition in target tissues, such as the liver. Here, we investigated microbiome × subacute PCB effects on the hepatic lipid composition of conventional and germ-free female mice exposed to 0, 6, or 30 mg/kg body weight of an environmental PCB mixture in sterile corn oil once daily for 3 consecutive days. Hepatic triacylglyceride and polar lipid levels were quantified using mass spectrometric methods following the subacute PCB exposure. The lipidomic analysis revealed no PCB effect on the hepatic levels. No microbiome effect was observed on levels of triacylglyceride and most polar lipid classes. The total hepatic levels of phosphatidylcholine (PC) and ether-phosphatidylcholine (ePC) lipids were lower in germ-free mice than the conventional mice from the same exposure group. Moreover, levels of several unsaturated PCs, such as PC(36:5) and PC(42:10), and ePCs, such as ePC(36:2) and ePC(4:2), were lower in germ-free than conventional female mice. Based on a KEGG pathway meta-analysis of RNA sequencing data, the ether lipid metabolism pathway is altered in the germ-free mouse liver. In contrast to the liver, extractable lipid levels, determined gravimetrically, differed in several tissues from naïve conventional vs. germ-free mice. Overall, microbiome × subacute PCB exposure effects on hepatic lipid composition are unlikely to affect PCB distribution into the mouse liver. Further studies are needed to assess how the different extractable lipid levels in other tissues alter PCB distribution in conventional vs. germ-free mice.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)

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P30 ES005605 United States ES NIEHS NIH HHS; R01 ES031098 United States ES NIEHS NIH HHS; P20 GM103418 United States GM NIGMS NIH HHS; R01 ES019487 United States ES NIEHS NIH HHS; R01 GM111381 United States GM NIGMS NIH HHS; P30 ES007033 United States ES NIEHS NIH HHS; R01 ES025708 United States ES NIEHS NIH HHS; P42 ES013661 United States ES NIEHS NIH HHS; R01 ES014901 United States ES NIEHS NIH HHS

Keywords: Enterotype; Lipidomics; Mus musculus; Persistent organic pollutant; Transcriptomics

DFC2HB4I0K (Polychlorinated Biphenyls)
0 (Phosphatidylcholines)

Date Created: 20240329 Date Completed: 20240430 Latest Revision: 20241122

20241122

PMC11579902

10.1016/j.tox.2024.153790

38552894