The obesogenic role of phthalates: A systematic review of mechanistic pathways (2018-2025)
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Ying Liu 1 2 , Xue Chen 2 , Liping Li 2 , Farrah Shafeera Ibrahim 3 , Emmy Hainida Khairul Ikram 1 4 *
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1 Center for Dietetics Studies, Faculty of Health Sciences Universiti Teknologi MARA, Bandar Puncak Alam, Selangor, MALAYSIA2 School of Public Health, Ningxia Medical University, Yinchuan, Ningxia, CHINA3 Department of Basic Sciences, Faculty of Health Sciences, Universiti Teknologi MARA, Puncak Alam Campus, Puncak Alam, Selangor, MALAYSIA4 Integrated Nutrition Sciences and Therapy Research Group, Faculty of Health Sciences, Universiti Teknologi MARA, Bandar Puncak Alam, Selangor, MALAYSIA* Corresponding Author

Abstract

Purpose: This systematic review synthesizes evidence on the mechanistic pathways through which phthalates act as obesogenic endocrine-disrupting chemicals. It focuses on molecular and cellular processes, including peroxisome proliferator-activated receptor gamma (PPARγ) activation, adipogenesis, adipokine dysregulation, oxidative stress, endocrine disruption, mitochondrial dysfunction, and epigenetic reprogramming, and integrates evidence from in-vitro, in-vivo, and human epidemiological studies published between 2018 and 2025.
Method: The review was conducted in accordance with PRISMA 2020. Searches were performed in PubMed, Scopus, Web of Science, and ScienceDirect using predefined keywords related to phthalates, obesity, adipogenesis, lipid metabolism, endocrine disruption, and epigenetics. After duplicate removal, title and abstract screening, and full-text eligibility assessment, 34 studies were included: 10 cellular or animal mechanistic studies, 14 mechanistic or epigenetic reviews, and 10 human epidemiological studies or meta-analyses with mechanistic discussion.
Findings: Across multiple models, phthalates, particularly di(2-ethylhexyl) phthalate and its metabolites, were associated with activation of PPARγ and other adipogenic transcription factors, enhanced adipocyte differentiation, disrupted adipokine balance, oxidative stress, adipose tissue inflammation, and endocrine dysregulation. Mechanistic and epigenetic reviews further suggest that phthalate exposure may induce DNA methylation changes, histone modification, and transgenerational effects, especially during critical developmental windows. Human cohort studies and meta-analyses generally support positive associations between phthalate exposure and adiposity, central obesity, and metabolic syndrome features, although heterogeneity, non-linear relationships, and sex-specific patterns remain evident.
Implications: The evidence supports a multi-pathway mechanistic model in which phthalates contribute to obesity through adipogenesis, inflammatory and mitochondrial dysfunction, hormonal disruption, and epigenetic programming. These findings provide a useful framework for regulatory risk assessment, public health prevention, and future mechanistic research on phthalate substitutes and mixed chemical exposures.

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article Type: Review Article

ELECTRON J GEN MED, Volume 23, Issue 3, June 2026, Article No: em734

https://doi.org/10.29333/ejgm/18583

Publication date: 22 May 2026

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Article Downloads: 3

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