Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation

Schaffert, Alexandra; Krieg, Laura; Weiner, Juliane; Schlichting, Rita; Ueberham, Elke; Karkossa, Isabel; Bauer, Mario; Landgraf, Kathrin; Junge, Kristin M.; Wabitsch, Martin; Lehmann, Jörg; Escher, Beate I.; Zenclussen, Ana Claudia; Körner, Antje; Blüher, Matthias; Heiker, John T.; Bergen, Martin von; Schubert, Kristin

doi:10.1016/j.envint.2021.106730

Cited by 31 publications

(34 citation statements)

References 82 publications

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“…In our experimental model, cells were exposed to TPA and DMT at levels mimicking those that might be obtained in adult humans with the consumption of foods contained in PET packages, similar to other findings reported in the literature [ 50 , 51 ] or environmentally relevant concentrations found in the blood of human subjects [ 25 , 26 ]. One has to take into consideration that intestinal absorption of 100% of the phthalates after oral ingestion may be hypothesized; as said before, the in silico ADME analysis showed intestinal absorption of p-phthalates ranging between 75% (TPA) and 90% (DMT) ( Table 1 ).…”

Section: Discussionmentioning

confidence: 81%

The p-Phthalates Terephthalic Acid and Dimethyl Terephthalate Used in the Manufacture of PET Induce In Vitro Adipocytes Dysfunction by Altering Adipogenesis and Thermogenesis Mechanisms

et al. 2022

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Public health concerns associated with the potential leaching of substances from Polyethylene terephthalate (PET) packaging have been raised due to the role of phthalates as endocrine-disrupting chemicals or obesogens. In particular, changes in the environment such as pH, temperature, and irradiation can improve contaminant migration from PET food packaging. In this study, the in vitro effects of p-phthalates terephthalic acid (TPA) and dimethyl terephthalate (DMT) on murine adipocytes (3T3-L1) were evaluated using concentrations that might be obtained in adult humans exposed to contaminated sources. TPA and, in particular, DMT exposure during 3T3-L1 differentiation increased the cellular lipid content and induced adipogenic markers PPAR-γ, C/EBPß, FABP4, and FASN, starting from low nanomolar concentrations. Interestingly, the adipogenic action of TPA- and DMT-induced PPAR-γ was reverted by ICI 182,780, a specific antagonist of the estrogen receptor. Furthermore, TPA and DMT affected adipocytes’ thermogenic program, reducing pAMPK and PGC-1α levels, and induced the NF-κB proinflammatory pathway. Given the observed effects of biologically relevant chronic concentrations of these p-phthalates and taking into account humans’ close and constant contact with plastics, it seems appropriate that ascertaining safe levels of TPA and DMT exposure is considered a high priority.

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Section: Discussionmentioning

confidence: 81%

The p-Phthalates Terephthalic Acid and Dimethyl Terephthalate Used in the Manufacture of PET Induce In Vitro Adipocytes Dysfunction by Altering Adipogenesis and Thermogenesis Mechanisms

et al. 2022

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“…Estrogen receptor pathways do not emerge as the main activation pathway for BPS, which could exert its obesogenic effects via PPARγ activation [51,58]. In this regard, Schaffert et al recently investigated the mode of action of BPA and four of its substitutes during the differentiation of human preadipocytes [73]. BPA, BPS, and BPF disrupted crucial metabolic functions and insulin signalling at low and environmentally relevant concentrations, and the effects were mediated via the inhibition of PPARγ.…”

Section: Discussionmentioning

confidence: 99%

The Mixture of Bisphenol-A and Its Substitutes Bisphenol-S and Bisphenol-F Exerts Obesogenic Activity on Human Adipose-Derived Stem Cells

Reina-Pérez

Olivas-Martínez

Mustieles

et al. 2022

Toxics

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Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and S (BPS), have previously shown in vitro obesogenic activity. This study was designed to investigate their combined effect on the adipogenic differentiation of human adipose-derived stem cells (hASCs). Cells were exposed for 14 days to an equimolar mixture of bisphenols (MIX) (range 10 nM–10 µM). Oil Red staining was used to measure intracellular lipid accumulation, quantitative real-time polymerase chain reaction (qRT-PCR) to study gene expression of adipogenic markers (PPARγ, C/EBPα, LPL, and FABP4), and Western Blot to determine their corresponding proteins. The MIX promoted intracellular lipid accumulation in a dose-dependent manner with a maximal response at 10 µM. Co-incubation with pure antiestrogen (ICI 182,780) inhibited lipid accumulation, suggesting that the effect was mediated by the estrogen receptor. The MIX also significantly altered the expression of PPARγ, C/EBPα, LPL, and FABP4 markers, observing a non-monotonic (U-shaped) dose-response, with maximal gene expression at 10 nM and 10 µM and lesser expression at 1 µM. This pattern was not observed when bisphenols were tested individually. Exposure to MIX (1–10 µM) also increased all encoded proteins except for FABP4, which showed no changes. Evaluation of the combined effect of relevant chemical mixtures is needed rather than single chemical testing.

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“…Numerous studies show that BPS has the same adipogenic properties as BPA [100][101][102][103][104]. Boucher et al compared the capacity of BPA and BPS to induce adipocyte differentiation [103].…”

Section: Bps Presents the Same Adipogenic Effect As Bpamentioning

confidence: 99%

“…An epidemiological study established a link between urinary concentrations of bisphenol AF (BPAF) and type II diabetes [91]. BPA substitutes, including BPS, BPB, BPF, and BPAF, were shown to disrupt metabolic functions and insulin signaling in adipocytes under low, environmentally relevant concentrations through the inhibition of the PPARγ pathway [102]. Kidani et al demonstrated that BPB, BPE and BPF decreased the amounts of intracellular and medium adiponectin [52].…”

Section: Other Bisphenolsmentioning

confidence: 99%

Are BPA Substitutes as Obesogenic as BPA?

Oliviero

Marmugi

Viguié

et al. 2022

IJMS

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Metabolic diseases, such as obesity, Type II diabetes and hepatic steatosis, are a significant public health concern affecting more than half a billion people worldwide. The prevalence of these diseases is constantly increasing in developed countries, affecting all age groups. The pathogenesis of metabolic diseases is complex and multifactorial. Inducer factors can either be genetic or linked to a sedentary lifestyle and/or consumption of high-fat and sugar diets. In 2002, a new concept of “environmental obesogens” emerged, suggesting that environmental chemicals could play an active role in the etiology of obesity. Bisphenol A (BPA), a xenoestrogen widely used in the plastic food packaging industry has been shown to affect many physiological functions and has been linked to reproductive, endocrine and metabolic disorders and cancer. Therefore, the widespread use of BPA during the last 30 years could have contributed to the increased incidence of metabolic diseases. BPA was banned in baby bottles in Canada in 2008 and in all food-oriented packaging in France from 1 January 2015. Since the BPA ban, substitutes with a similar structure and properties have been used by industrials even though their toxic potential is unknown. Bisphenol S has mainly replaced BPA in consumer products as reflected by the almost ubiquitous human exposure to this contaminant. This review focuses on the metabolic effects and targets of BPA and recent data, which suggest comparable effects of the structural analogs used as substitutes.

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Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation

Cited by 31 publications

References 82 publications

The p-Phthalates Terephthalic Acid and Dimethyl Terephthalate Used in the Manufacture of PET Induce In Vitro Adipocytes Dysfunction by Altering Adipogenesis and Thermogenesis Mechanisms

The p-Phthalates Terephthalic Acid and Dimethyl Terephthalate Used in the Manufacture of PET Induce In Vitro Adipocytes Dysfunction by Altering Adipogenesis and Thermogenesis Mechanisms

The Mixture of Bisphenol-A and Its Substitutes Bisphenol-S and Bisphenol-F Exerts Obesogenic Activity on Human Adipose-Derived Stem Cells

Are BPA Substitutes as Obesogenic as BPA?

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