Bisphenol F suppresses insulin-stimulated glucose metabolism in adipocytes by inhibiting IRS-1/PI3K/AKT pathway

Chen, Huiling; Li, Jiangbin; Zhang, Yanchao; Zhang, Wei; Li, Xing; Tang, Huanwen; Liu, Yungang; Li, Tianlan; He, Haoqi; Du, Bohai; Li, Li; Shi, Ming

doi:10.1016/j.ecoenv.2022.113201

Cited by 22 publications

(7 citation statements)

References 59 publications

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“…36 BPA could increase apelin levels in human ovarian cancer cells, 37 and bisphenol F (BPF), a substitute for bisphenol A (BPA), could decrease apelin levels in 3T3-L1 adipocytes. 38 In the present study, a 6-month exposure to BPA at an environmental level (0.25 μg/kg every other day) resulted in a significant increase in apelin levels in vivo, potentially indicating that lower-dose BPA exposure induces a hormetic effect. However, the serum apelin levels in the higher-dose BPA exposure group (25 μg/kg every other day) were similar to those in the normal control group.…”

Section: Discussionsupporting

confidence: 45%

Impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue

Liu,

Li,

Zhong

et al. 2023

Hum Exp Toxicol

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Background: Adipose tissue is a dynamic endocrine organ that plays a key role in regulating metabolic homeostasis. Previous studies confirmed that bisphenol A (BPA) or fructose can interfere with the function of adipose tissue. Nonetheless, knowledge on how exposure to BPA and fructose impacts energy metabolism in adipose tissue remains limited. Purpose: To determine impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue. Method: 57 energy metabolic intermediates in adipose tissue and 7 adipocytokines in serum from Sprague Dawley rats were examined after combined exposure to two levels of BPA (lower dose: 0.25, and higher dose: 25 μg/kg every other day) and 5% fructose for 6 months. Results: combined exposure to lower-dose BPA and fructose significantly increased omentin-1, pyruvic acid, adenosine triphosphate (ATP), adenosine monophosphate (AMP), inosine monophosphate (IMP), inosine, and l-lactate; however, these parameters were not significantly affected by higher-dose BPA combined with fructose. Interestingly, the level of succinate (an intermediate of the citric acid cycle) increased dose-dependently in adipose tissue, and the level of apelin 13 (a versatile adipocytokine) decreased dose-dependently in serum after combined exposure to BPA and fructose. Phosphoenolpyruvic acid, phenyl-lactate, and ornithine were significantly correlated with asprosin, omentin-1, apelin, apelin 13, and adiponectin, while l-tyrosine was significantly correlated with irisin and a-FABP under combined exposure to BPA and fructose. Conclusions: these findings indicated that lower-dose BPA combined with fructose could amplify the impact on glycolysis, energy storage, and purine nucleotide biosynthesis in adipose tissue, and adipocytokines, such as omentin-1 and apelin 13, may be related to metabolic interference induced by BPA and fructose exposure.

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Section: Discussionsupporting

confidence: 45%

Impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue

Liu,

Li,

Zhong

et al. 2023

Hum Exp Toxicol

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“…67 Bisphenol analogs dysregulate PI3K/Akt pathway which is implicated in many cellular processes including autophagy, apoptosis, glucose metabolism, cell proliferation, cell cycle progression, and even ovarian follicular development. 26,68,69 Further, PI3K/Akt pathway was shown to be directly inhibited by ROS terminating into increased apoptosis. 70 The PI3K/Akt pathway is also a critical signaling passage essential for transducing LH/ FSH signal.…”

Section: Discussionmentioning

confidence: 99%

“…In target tissues, insulin controls the activation of IR/PI3K/Akt pathway regulating GLUT‐4 vesicle translocation to the membrane for glucose utilization by the cells 67 . Bisphenol analogs dysregulate PI3K/Akt pathway which is implicated in many cellular processes including autophagy, apoptosis, glucose metabolism, cell proliferation, cell cycle progression, and even ovarian follicular development 26,68,69 . Further, PI3K/Akt pathway was shown to be directly inhibited by ROS terminating into increased apoptosis 70 .…”

Section: Discussionmentioning

confidence: 99%

BPS‐induced ovarian dysfunction: Protective actions of melatonin via modulation of SIRT‐1/Nrf2/NFĸB and IR/PI3K/pAkt/GLUT‐4 expressions in adult golden hamster

Pal

Sahu

Verma

et al. 2023

Journal of Pineal Research

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Ever‐increasing occurrence of plastic‐manufacturing industries leads to environmental pollution that has been associated with declined human health and increased incidence of compromised reproductive health. Female subfertility/infertility is a complex phenomenon and environmental toxicants as well as lifestyle factors have a crucial role to play. Bisphenol S (BPS) was believed to be a “safer” replacement of bisphenol A (BPA) but recent data documented its neurotoxic, hepatotoxic, nephrotoxic, and reprotoxic attributes. Hence based on the scarcity of reports, we investigated molecular insights into BPS‐induced ovarian dysfunction and protective actions of melatonin against it in adult golden hamsters, Mesocricetus auratus. Hamsters were administered with melatonin (3 mg/kg BW i.p. alternate days) and BPS (150 mg/kg BW orally every day) for 28 days. BPS treatment disrupted hypothalamo–pituitary–ovarian (HPO) axis as evident by reduced gonadotropins such as luteinizing hormone (LH) and follicle‐stimulating hormone (FSH), ovarian steroids such as estradiol (E2) and progesterone (P4), thyroid hormones namely triiodothyronine (T3) and thyroxine (T4) and melatonin levels along with their respective receptors (ERα, TRα, and MT‐1) thereby reducing ovarian folliculogenesis. BPS exposure also led to ovarian oxidative stress/inflammation by increasing reactive oxygen species and metabolic disturbances. However, melatonin supplementation to BPS restored ovarian folliculogenesis/steroidogenesis as indicated by increased number of growing follicles/corpora lutea and E2/P4 levels. Further, melatonin also stimulated key redox/survival markers such as silent information regulator of transcript‐1 (SIRT‐1), forkhead box O‐1 (FOXO‐1), nuclear factor E2‐related factor‐2 (Nrf2), and phosphoinositide 3‐kinase/protein kinase B (PI3K/pAkt) expressions along with enhanced ovarian antioxidant capacity. Moreover, melatonin treatment reduced inflammatory load including ovarian nuclear factor kappa‐B (NFĸB), cyclooxygenase‐2 (COX‐2), and inducible nitric oxide synthase (iNOS) expressions, serum tumor necrosis factor α (TNFα), C‐reactive protein (CRP) and nitrite–nitrate levels as well as upregulated ovarian insulin receptor (IR), glucose uptake transporter‐4 (GLUT‐4), connexin‐43, and proliferating cell nuclear antigen (PCNA) expressions in ovary thereby ameliorating inflammatory and metabolic alterations due to BPS. In conclusion, we found severe deleterious impact of BPS on ovary while melatonin treatment protected ovarian physiology from these detrimental changes suggesting it to be a potential preemptive candidate against environmental toxicant‐compromised female reproductive health.

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“…However, this might be an adjustment for sensitive populations, such as low-income individuals who are prone to overexposure. In their study, the exposure of BPF before and after adjustment was 0.4 versus 0.3 ng/mL, respectively, which was much less than the BPA exposure of 1.5 versus 1.1 ng/mL [ 52 ], and studies have shown that BPF can interfere with the IRS-1/PI3K/AKT signal transduction pathway and subsequently affect the insulin-dependent glucose metabolism pathway of adipocytes (3T3-L1 adipocytes), resulting in obesity [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Association Between Urinary Bisphenols and Body Composition Among American Adults: Cross-Sectional National Health and Nutrition Examination Survey Study

Li,

Zhang,

Zhang

et al. 2023

JMIR Public Health Surveill

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Background Bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) are widely used in various consumer products. They are environmental contaminants with estrogenic properties that have been linked to various health outcomes. Understanding their impact on body composition is crucial for identifying potential health risks and developing preventive strategies. However, most current studies have only focused on their relationship with BMI. Objective This study aimed to investigate the association between urinary levels of BPA, BPS, and BPF and body composition, including BMI, lean mass, and fat mass, in a large population-based sample. Methods We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey 2003-2016. Body composition data were assessed using dual-energy X-ray absorptiometry, which provided precise measurements of lean mass, fat mass, and other indicators. We used multivariate linear regression models to estimate the associations, adjusting for potential confounders such as age, gender, race, socioeconomic factors, and lifestyle variables. Results The results revealed significant associations between bisphenol exposure and body composition. After adjusting for covariates, BPS showed a positive association with BMI, with quartiles 3 and 4 having 0.91 (95% CI 0.34-1.48) and 1.15 (95% CI 0.55-1.74) higher BMI, respectively, compared with quartile 1 (P<.001). BPA was negatively associated with total lean mass (TLM) and appendicular lean mass, with quartiles 2, 3, and 4 having –7.85 (95% CI –11.44 to –4.25), –12.33 (95% CI –16.12 to –8.54), and –11.08 (95% CI –15.16 to –7.01) lower TLM, respectively, compared with quartile 1 (P<.001). BPS was negatively associated with TLM, with quartiles 3 (β=–10.53, 95% CI –16.98 to –4.08) and 4 (β=–11.14, 95% CI –17.83 to –4.45) having significantly lower TLM (P=.005). Both BPA and BPS showed a positive dose-response relationship with trunk fat (BPA: P=.002; BPS: P<.001) and total fat (BPA: P<.001; BPS: P=.01). No significant association was found between BPF and any body composition parameter. Conclusions This large-sample study highlights the associations between urinary levels of BPA and BPS and alterations in body composition, including changes in lean mass, fat mass, and regional fat distribution. These findings underscore the importance of understanding the potential health risks associated with bisphenol exposure and emphasize the need for targeted interventions to mitigate adverse effects on body composition.

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Bisphenol F suppresses insulin-stimulated glucose metabolism in adipocytes by inhibiting IRS-1/PI3K/AKT pathway

Cited by 22 publications

References 59 publications

Impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue

Impact of combined chronic exposure to low-dose bisphenol A and fructose on serum adipocytokines and the energy target metabolome in white adipose tissue

BPS‐induced ovarian dysfunction: Protective actions of melatonin via modulation of SIRT‐1/Nrf2/NFĸB and IR/PI3K/pAkt/GLUT‐4 expressions in adult golden hamster

Association Between Urinary Bisphenols and Body Composition Among American Adults: Cross-Sectional National Health and Nutrition Examination Survey Study

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