Facilitation of adipocyte differentiation of 3T3-L1 cells by debrominated tetrabromobisphenol A compounds detected in Japanese breast milk

Akiyama, Ema; Kakutani, Hideki; Nakao, Teruyuki; Motomura, Yuka; Takano, Yuki; Sorakubo, Ryota; Mizuno, Ayami; Aozasa, Osamu; Tachibana, Keisuke; Doi, Takefumi; Ohta, Souichi

doi:10.1016/j.envres.2015.03.035

Cited by 35 publications

(36 citation statements)

References 41 publications

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“…Regarding tetrabromobisphenol-A (TBBPA), the brominated analogue of BPA, Riu et al [55] studied the effect of this compound on cell differentiation towards adipocytes in the NIH3T3-L1 cell line and determined that TBBPA presents specific binding with the protein PPARc, activating it, which ultimately favored the accumulation of triglycerides in the cell. Similar results were also obtained in the studies of Akiyama et al [68], who first demonstrated the presence of TBBPA in human milk, but also determined the proadipogenic activity of TBBAP and its brominated derivatives in 3T3-L1 cells.…”

Section: Human Mesenchymal Cellssupporting

confidence: 88%

Adipogenesis Regulation and Endocrine Disruptors: Emerging Insights in Obesity

González-Casanova

Pertuz-Cruz

Caicedo-Ortega

et al. 2020

BioMed Research International

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Endocrine disruptors (EDs) are defined as environmental pollutants capable of interfering with the functioning of the hormonal system. They are environmentally distributed as synthetic fertilizers, electronic waste, and several food additives that are part of the food chain. They can be considered as obesogenic compounds since they have the capacity to influence cellular events related to adipose tissue, altering lipid metabolism and adipogenesis processes. This review will present the latest scientific evidence of different EDs such as persistent organic pollutants (POPs), heavy metals, “nonpersistent” phenolic compounds, triclosan, polybrominated diphenyl ethers (PBDEs), and smoke-derived compounds (benzo -alpha-pyrene) and their influence on the differentiation processes towards adipocytes in both in vitro and in vivo models.

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Section: Human Mesenchymal Cellssupporting

confidence: 88%

Adipogenesis Regulation and Endocrine Disruptors: Emerging Insights in Obesity

González-Casanova

Pertuz-Cruz

Caicedo-Ortega

et al. 2020

BioMed Research International

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“…The effect of EDCs seems to be higher in the fetus and in infants than in adults. In addition, we previously observed contamination of EDCs, such as TBBPA and dioxins, in human breast milk and in the body; the average concentration of TBBPA in a Japanese mother’s breast milk was 1.9 ng/g lipid, and polychlorinated dibenzo- p -dioxins and dibenzofurans (PCDDs/DFs: 17 congeners) and coplanar polychlorinated biphenyls (Co-PCBs: 14 congeners) were 3.6 and 3.5 pg TEQ/g lipid, respectively [ [18] , [19] , [20] , [21] ]. The contamination levels in human milk have been widely studied to provide a good indicator of overall human exposure, especially for infants.…”

Section: Introductionmentioning

confidence: 91%

Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD

et al. 2018

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People are frequently and unintentionally exposed to many chemical compounds, such as environmental pollutants and endocrine-disrupting chemicals (EDCs), in food and from the atmosphere. In particular, endocrine-disrupting TBBPA and dioxins are found in human breast milk and in the body. Conventional studies evaluate toxicity by administering a single substance to cells or animals, but evaluation of the toxicity of mixtures of these ingested compounds is essential for “true” toxicological assessment. We evaluated toxic effects in vitro using human mesenchymal stem cells (hMSCs). TBBPA increased the number of lipid droplets, and upregulated the expression of adipocyte-related mRNA, aP2 and LPL, through a PPARγ-dependent mechanism. TCDD suppressed lipid droplets and adipocyte-related mRNA levels. Adipocyte differentiation was stimulated by TBBPA and inhibited by TCDD in a dose-dependent manner. TBBPA did not influence osteoblast differentiation, but TCDD suppressed ALP staining and activity, calcium deposition, and osteoblast-related mRNA levels. In a mixture of TBBPA and TCDD, TBBPA inhibited TCDD suppression of adipocyte and osteoblast differentiation in a dose-dependent manner. Interestingly, we observed lipid droplets in TBBPA-treated cells differentiated into osteoblasts. These results suggest that TBBPA and TCDD disrupted differentiation into adipocytes and osteoblasts and contributes to a more complete toxicological understanding of exposure to these chemical substances.

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“…TCBPA was generally the most active chemical, potentially due to greater inhibition of TR or activation of PPARγ 57 58 . TBBPA, TCBPA, and BPA have been previously reported to increase triglyceride accumulation and/or cell proliferation in 3T3-L1 cells, though the maximal rosiglitazone response is often not provided for ease of translation to relative effect and subsequent comparison to other studies 35 45 57 59 . BPA has been shown previously to increase adipogenic gene expression (aP2) through a non-classical ER-mediated mechanism 60 , suggesting that these mechanisms could account for the disparate response.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Adipogenic Chemicals in Three Different Cell Culture Systems: Implications for Reproducibility Based on Cell Source and Handling

Kassotis

Masse

Kim

et al. 2017

Sci Rep

120

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The potential for chemical exposures to exacerbate the development and/or prevalence of metabolic disorders, such as obesity, is currently of great societal concern. Various in vitro assays are available to assess adipocyte differentiation, though little work has been done to standardize protocols and compare models effectively. This study compares several adipogenic cell culture systems under a variety of conditions to assess variability in responses. Two sources of 3T3-L1 preadipocytes as well as OP9 preadipocytes were assessed for cell proliferation and triglyceride accumulation following different induction periods and using various tissue culture plates. Both cell line and cell source had a significant impact on potencies and efficacies of adipogenic chemicals. Gene expression analyses suggested that differential expression of nuclear receptors involved in adipogenesis underlie the differences between OP9 and 3T3-L1 cells; however, there were also differences based on 3T3-L1 cell source. Induction period modulated potency and efficacy of response depending on cell line and test chemical, and large variations were observed in triglyceride accumulation and cell proliferation between brands of tissue culture plates. Our results suggest that the selection of a cell system and differentiation protocol significantly impacts the detection of adipogenic chemicals, and therefore, influences reproducibility of these studies.

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Facilitation of adipocyte differentiation of 3T3-L1 cells by debrominated tetrabromobisphenol A compounds detected in Japanese breast milk

Cited by 35 publications

References 41 publications

Adipogenesis Regulation and Endocrine Disruptors: Emerging Insights in Obesity

Adipogenesis Regulation and Endocrine Disruptors: Emerging Insights in Obesity

Complex toxicity as disruption of adipocyte or osteoblast differentiation in human mesenchymal stem cells under the mixed condition of TBBPA and TCDD

Characterization of Adipogenic Chemicals in Three Different Cell Culture Systems: Implications for Reproducibility Based on Cell Source and Handling

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