PFAS and Potential Adverse Effects on Bone and Adipose Tissue through Interactions with PPARγ
Open accessAbstract
Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a widely dispersed, broad class of synthetic chemicals with diverse biological effects, including effects on adipose and bone differentiation. PFAS most commonly occur as mixtures and only rarely, if ever, as single environmental contaminants. This poses significant regulatory questions and a pronounced need for chemical risk assessments, analytical methods, and technological solutions to reduce the risk to public and environmental health. The effects of PFAS on biological systems may be complex. Each may have several molecular targets initiating multiple biochemical events leading to a number of different adverse outcomes. An exposure to mixtures or coexposures of PFAS complicates the picture further. This review illustrates how PFAS target peroxisome proliferator-activated receptors. Additionally, we describe how such activation leads to changes in cell differentiation and bone development that contributes to metabolic disorder and bone weakness. This discussion sheds light on the importance of seemingly modest outcomes observed in test animals and highlights why the most sensitive end points identified in some chemical risk assessments are significant from a public health perspective.
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PPARs are concentrated in tissues with high metabolic demand, including the liver, kidneys, and brain, and serve as important regulators of the immune system.
“PPARs are concentrated in tissues with high metabolic demand, including the liver, kidneys, and brain, and serve as important regulators of the immune system”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Kirk et al., 2021
In “Brief Introduction to Peroxisome Proliferator–Activated Receptors” (indexed as Abstract; no page supplied), the paper says PPARα is concentrated in metabolically demanding tissues including the liver and kidney, but lists the heart and brown adipose tissue—not the brain. In “Other PPARγ-Influenced Effects” (also indexed as Abstract; no page supplied), it describes PPARγ’s role in innate immune responsiveness. The claim combines findings about different PPAR subtypes and does not support the brain as a site of concentration. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPFAS exposure may have important implications for the treatment of certain ailments, such as brain cancer, epilepsy, and depression, through restriction of drug delivery.
“PFAS exposure may have important implications for the treatment of certain ailments, such as brain cancer, epilepsy, and depression (More et al., 2017; Kirk et al., 2021), through restriction of drug delivery.”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Kirk et al., 2021
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References 153 · Cited by 90
Research works printed but not linked: 5
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- Authors
- Kirk, A. B., Michelsen-Correa, S., Rosen, C., Martin, C. F., & Blumberg, B.
- Affiliations
- Environmental Protection Agency (US)
- Tufts University School of Medicine, Boston, Massachusetts 02111, USA
- Texas Tech University (US)
- University of California, Irvine (US)
- Corresponding author
- Kirk, Andrea B
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2021-09-04
- Volume
- 162
- Issue
- 12
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC9034324
- OpenAlex
- W3197799900
- Cited by
- 90
- References
- 153
- Citations by year
- 2026: 17 · 2025: 30 · 2024: 15 · 2023: 17 · 2022: 11
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Endocrinology (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- per- and polyfluoroalkyl substances, PFAS, PPARγ, skeletal development, adipose tissue, adipogenesis, bone differentiation, metabolic disorders, bone fragility, chemical mixtures, combined exposure, chemical risk assessment, endocrine disruption
- MeSH terms
- Adipose Tissue, Animals, Bone and Bones, Environmental Pollutants, Fluorocarbons, Humans, Protein Binding, PPAR gamma
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