Characterization of POP mixture redistribution and identification of their molecular signature in xenografted fat mice

Persistent organic pollutants (POPs) are associated with many adverse health effects in humans, including cancers, immune, reproductive, neurological disorders and metabolic diseases. These chemicals are known to accumulate in fatty tissues, from which they can be released in other tissue compartments of living organisms, in particular, upon weight loss. This dynamic distribution of POPs remains, however poorly investigated. In this study, a xenografted POP-contaminated adipose tissue (AT) model was used to assess 1) their concentrations in the ATs, the liver and the brain and 2) their associated effects by transcriptomics, metabolomics and lipidomics approaches. In the ATs, the liver and the brain of mice grafted with POP-contaminated fat pad, most of POPs were detected 3 days and 21 days after the graft with the highest concentrations in the ATs and the lowest concentrations in the brain. Conversely, per- and polyfluoroalkyl substances presented a distinct profile as they persist in the liver but not in the ATs or in the brain. In the AT of POP-exposed mice, the most dysregulated pathways were related to mitochondrial functions, endobiotic (carbohydrate, lipid, amino acid) and xenobiotic metabolism and inflammatory response. In the liver of grafted mice, many pathways related to mitochondrial functions and metabolism were dysregulated. These results support that realistic mixture of POPs that accumulate in AT and liver induces a systemic metabolic dysfunction which may represent the mechanisms by which the POPs can promote metabolic diseases such as obesity, type 2 diabetes and cardiovascular diseases.

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Publication Details

Journal
Environmental Pollution
Published
2025-04-12
DOI
https://doi.org/10.1016/j.envpol.2025.126239
Primary Topic
Per- and polyfluoroalkyl substances research
Type
article
Field-Weighted Citation Impact
0.00

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article

Characterization of POP mixture redistribution and identification of their molecular signature in xenografted fat mice

Étienne Blanc, Covadonga Lucas‐Torres, Haidar Djemai, Patricia Margaritte‐Jeannin et al.
Environmental Pollution
Per- and polyfluoroalkyl substances research
article

Characterization of POP mixture redistribution and identification of their molecular signature in xenografted fat mice

Étienne Blanc, Covadonga Lucas‐Torres, Haidar Djemai, Patricia Margaritte‐Jeannin, Florence Jornod, Bruno Le Bizec, Germán Cano-Sancho, Gildas Bertho, Nicolas Giraud, Sadia Ouzia, Justine Massias, Xavier Coumoul, Philippe Noirez, Karine Audouze, Layale Youssef, Jean‐Philippe Antignac, Min Ji Kim, Philippe Marchand, Yann Guitton, Théo Jamay
article en

Abstract

Persistent organic pollutants (POPs) are associated with many adverse health effects in humans, including cancers, immune, reproductive, neurological disorders and metabolic diseases. These chemicals are known to accumulate in fatty tissues, from which they can be released in other tissue compartments of living organisms, in particular, upon weight loss. This dynamic distribution of POPs remains, however poorly investigated. In this study, a xenografted POP-contaminated adipose tissue (AT) model was used to assess 1) their concentrations in the ATs, the liver and the brain and 2) their associated effects by transcriptomics, metabolomics and lipidomics approaches. In the ATs, the liver and the brain of mice grafted with POP-contaminated fat pad, most of POPs were detected 3 days and 21 days after the graft with the highest concentrations in the ATs and the lowest concentrations in the brain. Conversely, per- and polyfluoroalkyl substances presented a distinct profile as they persist in the liver but not in the ATs or in the brain. In the AT of POP-exposed mice, the most dysregulated pathways were related to mitochondrial functions, endobiotic (carbohydrate, lipid, amino acid) and xenobiotic metabolism and inflammatory response. In the liver of grafted mice, many pathways related to mitochondrial functions and metabolism were dysregulated. These results support that realistic mixture of POPs that accumulate in AT and liver induces a systemic metabolic dysfunction which may represent the mechanisms by which the POPs can promote metabolic diseases such as obesity, type 2 diabetes and cardiovascular diseases.

Environmental PollutionVol. 374
Délégation Paris 5 (FR), University of Jordan (JO), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université du Québec à Montréal (CA), Université Paris Cité (FR), Sorbonne Université (FR), Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR), Université Sorbonne Paris Nord (FR), Sorbonne Paris Cité (FR), Laboratoire D'étude des Résidus et Contaminants Dans les Aliments (FR), Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques (FR), Oniris (FR), Université de Reims Champagne-Ardenne (FR)
Agence Nationale de la Recherche, Conseil Régional des Pays de la Loire
Zero hunger
Openalex Percentile: Top 92%
Per- and polyfluoroalkyl substances research
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