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Metabolomic-based assessment reveals dysregulation of lipid profiles in human liver cells exposed to environmental obesogens.
Toxicol Appl Pharmacol. 2020 07 01; 398:115009.TA

Abstract

Significant attention has been given to the potential of environmental chemicals to disrupt lipid homeostasis at the cellular level. These chemicals, classified as obesogens, are abundantly used in a wide variety of consumer products. However, there is a significant lack of information regarding the mechanisms by which environmental exposure can contribute to the onset of obesity and non-alcoholic fatty liver disease (NAFLD). Several studies have described the interaction of potential obesogens with lipid-related peroxisome proliferator-activated receptors (PPAR). However, no studies have quantified the degree of modification to lipidomic profiles in relevant human models, making it difficult to directly link PPAR agonists to the onset of lipid-related diseases. A quantitative metabolomic approach was used to examine the dysregulation of lipid metabolism in human liver cells upon exposure to potential obesogenic compounds. The chemicals rosiglitazone, perfluorooctanoic acid, di-2-ethylexylphthalate, and tributyltin significantly increased total lipids in liver cells, being diglycerides, triglycerides and phosphatidylcholines the most prominent. Contrarily, perfluorooctane sulfonic acid and the pharmaceutical fenofibrate appeared to lower total lipid concentrations, especially those belonging to the acylcarnitine, ceramide, triglyceride, and phosphatidylcholine groups. Fluorescence microscopy analysis for cellular neutral lipids revealed significant lipid bioaccumulation upon exposure to obesogens at environmentally relevant concentrations. This integrated omics analysis provides unique mechanistic insight into the potential of these environmental pollutants to promote diseases like obesity and NAFLD. Furthermore, this study provides a significant contribution to advance the understanding of molecular signatures related to obesogenic chemicals and to the development of alternatives to in vivo experimentation.

Authors+Show Affiliations

Department of Environmental Science, Baylor University, Waco, TX 76798, United States of America.Department of Biology, Baylor University, Waco, TX 76798, United States of America.Mass Spectrometry Center, Baylor University, Waco, TX 76798, United States of America.Department of Environmental Science, Baylor University, Waco, TX 76798, United States of America. Electronic address: Ramon_Lavado@baylor.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32353385

Citation

Franco, Marco E., et al. "Metabolomic-based Assessment Reveals Dysregulation of Lipid Profiles in Human Liver Cells Exposed to Environmental Obesogens." Toxicology and Applied Pharmacology, vol. 398, 2020, p. 115009.
Franco ME, Fernandez-Luna MT, Ramirez AJ, et al. Metabolomic-based assessment reveals dysregulation of lipid profiles in human liver cells exposed to environmental obesogens. Toxicol Appl Pharmacol. 2020;398:115009.
Franco, M. E., Fernandez-Luna, M. T., Ramirez, A. J., & Lavado, R. (2020). Metabolomic-based assessment reveals dysregulation of lipid profiles in human liver cells exposed to environmental obesogens. Toxicology and Applied Pharmacology, 398, 115009. https://doi.org/10.1016/j.taap.2020.115009
Franco ME, et al. Metabolomic-based Assessment Reveals Dysregulation of Lipid Profiles in Human Liver Cells Exposed to Environmental Obesogens. Toxicol Appl Pharmacol. 2020 07 1;398:115009. PubMed PMID: 32353385.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metabolomic-based assessment reveals dysregulation of lipid profiles in human liver cells exposed to environmental obesogens. AU - Franco,Marco E, AU - Fernandez-Luna,Maria T, AU - Ramirez,Alejandro J, AU - Lavado,Ramon, Y1 - 2020/04/27/ PY - 2020/02/10/received PY - 2020/04/10/revised PY - 2020/04/12/accepted PY - 2020/5/1/pubmed PY - 2020/5/1/medline PY - 2020/5/1/entrez KW - Cytotoxicity KW - HepaRG cell line KW - Lipidomics KW - Metabolomics KW - Obesogens SP - 115009 EP - 115009 JF - Toxicology and applied pharmacology JO - Toxicol. Appl. Pharmacol. VL - 398 N2 - Significant attention has been given to the potential of environmental chemicals to disrupt lipid homeostasis at the cellular level. These chemicals, classified as obesogens, are abundantly used in a wide variety of consumer products. However, there is a significant lack of information regarding the mechanisms by which environmental exposure can contribute to the onset of obesity and non-alcoholic fatty liver disease (NAFLD). Several studies have described the interaction of potential obesogens with lipid-related peroxisome proliferator-activated receptors (PPAR). However, no studies have quantified the degree of modification to lipidomic profiles in relevant human models, making it difficult to directly link PPAR agonists to the onset of lipid-related diseases. A quantitative metabolomic approach was used to examine the dysregulation of lipid metabolism in human liver cells upon exposure to potential obesogenic compounds. The chemicals rosiglitazone, perfluorooctanoic acid, di-2-ethylexylphthalate, and tributyltin significantly increased total lipids in liver cells, being diglycerides, triglycerides and phosphatidylcholines the most prominent. Contrarily, perfluorooctane sulfonic acid and the pharmaceutical fenofibrate appeared to lower total lipid concentrations, especially those belonging to the acylcarnitine, ceramide, triglyceride, and phosphatidylcholine groups. Fluorescence microscopy analysis for cellular neutral lipids revealed significant lipid bioaccumulation upon exposure to obesogens at environmentally relevant concentrations. This integrated omics analysis provides unique mechanistic insight into the potential of these environmental pollutants to promote diseases like obesity and NAFLD. Furthermore, this study provides a significant contribution to advance the understanding of molecular signatures related to obesogenic chemicals and to the development of alternatives to in vivo experimentation. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/32353385/Metabolomic-based_assessment_reveals_dysregulation_of_lipid_profiles_in_human_liver_cells_exposed_to_environmental_obesogens L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(20)30133-2 DB - PRIME DP - Unbound Medicine ER -
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