Bisphenol AF promotes inflammation in human white adipocytes

Chernis, Natasha; Masschelin, Peter M.; Cox, Aaron R.; Hartig, Sean M.

doi:10.1152/ajpcell.00175.2019

Cited by 14 publications

(6 citation statements)

References 72 publications

(85 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BPAF disrupts lipid and carbohydrate metabolism in adipocytes and activates inflammatory signaling pathways that degrade metabolic activity in human fat cells. BPAF also increases the expression of critical adipogenic markers in murine preadipocytes [88,89]. While our study did not examine these signaling pathways, our results are consistent with these findings.…”

Section: Discussionsupporting

confidence: 90%

“…For BPAF, this effective dose was 1,000-fold lower than that of BPA, highlighting its increased potency. These specific trends among bisphenol potencies and toxicities are consistent among ours and other's findings when exploring the effects of the compounds on adipogenesis, embryo development and cell division, and cytotoxicity and apoptosis in human stem cells [63,[68][69][70][71]80,88,89].…”

Section: Discussionsupporting

confidence: 90%

“…To date, no studies have explored the levels of TMBPF in the environment or human fluids, likely because of its recent use. It is of note that in the relatively higher doses of BPA and BPAF and all doses of TMBPF tested, there was a correlation between decreased adipogenesis and increased apoptosis, indicating some likely toxicity even at these relatively low, environmentally-relevant doses.Previous studies have examined the endocrine-disrupting actions of BPS and BPAF and found they increase adipogenesis and disrupt the metabolic functioning of both mature adipocytes and preadipocytes [80,83,88,89]. BPAF disrupts lipid and carbohydrate metabolism in adipocytes and activates inflammatory signaling pathways that degrade metabolic activity in human fat cells.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

BPA, BPAF and TMBPF Alter Adipogenesis and Fat Accumulation in Human Mesenchymal Stem Cells, with Implications for Obesity

Cohen

Cohenour

Harnett

et al. 2021

IJMS

View full text Add to dashboard Cite

Bisphenol A (BPA) is an endocrine-disrupting chemical used in the production of plastics, and is linked to developmental, reproductive, and metabolic disorders including obesity. Manufacturers have begun using ‘BPA-free’ alternatives instead of BPA in many consumer products. However, these alternatives have had much less testing and oversight, yet they are already being mass-produced and used across industries from plastics to food-contact coatings. Here, we used human female adipose-derived stem cells (hASCs), a type of adult mesenchymal stem cell, to compare the effects of BPA and BPA alternatives on adipogenesis or fat cell development in vitro. We focused on two commonly used BPA replacements, bisphenol AF (BPAF) and tetramethyl bisphenol F (TMBPF; monomer of the new valPure V70 food-contact coating). Human ASCs were differentiated into adipocytes using chemically defined media in the presence of control differentiation media with and without 17β-estradiol (E2; 10 μM), or with increasing doses of BPA (0, 0.1 and 1 μM), BPAF (0, 0.1, 1 and 10 nM), or TMBPF (0, 0.01 and 0.1 μM). After differentiation, the cells were stained and imaged to visualize and quantify the accumulation of lipid vacuoles and number of developing fat cells. Treated cells were also examined for cell viability and apoptosis (programmed cell death) using the respective cellular assays. Similar to E2, BPA at 0.1 μM and BPAF at 0.1 nM, significantly increased adipogenesis and lipid production by 20% compared to control differentiated cells (based on total lipid vacuole number to cell number ratios), whereas higher levels of BPA and BPAF significantly decreased adipogenesis (P < 0.005). All tested doses of TMBPF significantly reduced adipogenesis and lipid production by 30–40%, likely at least partially through toxic effects on stem cells, as viable cell numbers decreased and apoptosis levels increased throughout differentiation. These findings indicate that low, environmentally-relevant doses of BPA, BPAF, and TMBPF have significant effects on fat cell development and lipid accumulation, with TMBPF having non-estrogenic, anti-adipogenic effects. These and other recent results may provide a potential cellular mechanism between exposure to bisphenols and human obesity, and underscore the likely impact of these chemicals on fat development in vivo.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

BPA, BPAF and TMBPF Alter Adipogenesis and Fat Accumulation in Human Mesenchymal Stem Cells, with Implications for Obesity

Cohen

Cohenour

Harnett

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…RELA is a relevant transcription factor associated with adipocyte inflammation [ 81 ] that inhibits adipogenesis and accumulation of lipids in adipocytes [ 82 ]. The activation of STAT1 transcription factor inhibits adipogenesis and promotes adipocyte and adipose tissue inflammation [ 83 , 84 , 85 , 86 , 87 , 88 ]. Isolated mature adipocytes from obese individuals had increased expression of mitogen-activated protein 4 kinase 4 (MAP4K4), which is known to inhibit PPARγ transcriptional activity, adipogenesis, and insulin-stimulated glucose transport [ 89 , 90 ].…”

Section: Resultsmentioning

confidence: 99%

The Combined Partial Knockdown of CBS and MPST Genes Induces Inflammation, Impairs Adipocyte Function-Related Gene Expression and Disrupts Protein Persulfidation in Human Adipocytes

Latorre

Aroca²,

Fernández-Real³

et al. 2022

Antioxidants

View full text Add to dashboard Cite

Recent studies in mice and humans demonstrated the relevance of H2S synthesising enzymes, such as CTH, CBS, and MPST, in the physiology of adipose tissue and the differentiation of preadipocyte into adipocytes. Here, our objective was to investigate the combined role of CTH, CBS, and MPST in the preservation of adipocyte protein persulfidation and adipogenesis. Combined partial CTH, CBS, and MPST gene knockdown was achieved treating fully human adipocytes with siRNAs against these transcripts (siRNA_MIX). Adipocyte protein persulfidation was analyzed using label-free quantitative mass spectrometry coupled with a dimedone-switch method for protein labeling and purification. Proteomic analysis quantified 216 proteins with statistically different levels of persulfidation in KD cells compared to control adipocytes. In fully differentiated adipocytes, CBS and MPST mRNA and protein levels were abundant, while CTH expression was very low. It is noteworthy that siRNA_MIX administration resulted in a significant decrease in CBS and MPST expression, without impacting on CTH. The combined partial knockdown of the CBS and MPST genes resulted in reduced cellular sulfide levels in parallel to decreased expression of relevant genes for adipocyte biology, including adipogenesis, mitochondrial biogenesis, and lipogenesis, but increased proinflammatory- and senescence-related genes. It should be noted that the combined partial knockdown of CBS and MPST genes also led to a significant disruption in the persulfidation pattern of the adipocyte proteins. Although among the less persulfidated proteins, we identified several relevant proteins for adipocyte adipogenesis and function, among the most persulfidated, key mediators of adipocyte inflammation and dysfunction as well as some proteins that might play a positive role in adipogenesis were found. In conclusion, the current study indicates that the combined partial elimination of CBS and MPST (but not CTH) in adipocytes affects the expression of genes related to the maintenance of adipocyte function and promotes inflammation, possibly by altering the pattern of protein persulfidation in these cells, suggesting that these enzymes were required for the functional maintenance of adipocytes.

show abstract

“…Immunotoxic effects of many environmental and occupational chemical compounds have long been recognized [16]. Emerging evidence from experimental and population studies demonstrates the ability of a broad range of xenobiotics to interact with immunological pathways [17][18][19][20]. Thus, we hypothesize that specific immune response mechanisms may be synergistically affected by chemical exposures and SARS-CoV-2, resulting in increased severity of the disease.…”

Section: Introductionmentioning

confidence: 93%

Chemical Exposures Affect Innate Immune Response to SARS-CoV-2

Arowolo

Pobezinsky

Suvorov

2021

IJMS

View full text Add to dashboard Cite

Severe outcomes of COVID-19 are associated with pathological response of the immune system to the SARS-CoV-2 infection. Emerging evidence suggests that an interaction may exist between COVID-19 pathogenesis and a broad range of xenobiotics, resulting in significant increases in death rates in highly exposed populations. Therefore, a better understanding of the molecular basis of the interaction between SARS-CoV-2 infection and chemical exposures may open opportunities for better preventive and therapeutic interventions. We attempted to gain mechanistic knowledge on the interaction between SARS-CoV-2 infection and chemical exposures using an in silico approach, where we identified genes and molecular pathways affected by both chemical exposures and SARS-CoV-2 in human immune cells (T-cells, B-cells, NK-cells, dendritic, and monocyte cells). Our findings demonstrate for the first time that overlapping molecular mechanisms affected by a broad range of chemical exposures and COVID-19 are linked to IFN type I/II signaling pathways and the process of antigen presentation. Based on our data, we also predict that exposures to various chemical compounds will predominantly impact the population of monocytes during the response against COVID-19.

show abstract

Bisphenol AF promotes inflammation in human white adipocytes

Cited by 14 publications

References 72 publications

BPA, BPAF and TMBPF Alter Adipogenesis and Fat Accumulation in Human Mesenchymal Stem Cells, with Implications for Obesity

BPA, BPAF and TMBPF Alter Adipogenesis and Fat Accumulation in Human Mesenchymal Stem Cells, with Implications for Obesity

The Combined Partial Knockdown of CBS and MPST Genes Induces Inflammation, Impairs Adipocyte Function-Related Gene Expression and Disrupts Protein Persulfidation in Human Adipocytes

Chemical Exposures Affect Innate Immune Response to SARS-CoV-2

Contact Info

Product

Resources

About