Bisphenol A induces Pomc gene expression through neuroinflammatory and PPARγ nuclear receptor-mediated mechanisms in POMC-expressing hypothalamic neuronal models

Salehi, Ashkan; Loganathan, Neruja; Belsham, Denise D.

doi:10.1016/j.mce.2018.08.009

Cited by 23 publications

(16 citation statements)

References 53 publications

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“…In terms of other EDCs, a replacement compound for BPA, bisphenol S, also increased Agrp with no change in Pomc, Npy or Cart, in male mice (no females examined) (Rezg, Abot, Mornagui, Aydi, & Knauf, 2018). In comparison, perinatal BPA-exposed mice had a reduction in Pomc with no change in Agrp, while in another study, BPA increased Pomc potentially through a PPARγ-mediated mechanism (MacKay, Patterson, & Abizaid, 2017;Salehi, Loganathan, & Belsham, 2019). This could potentially explain the increase in total T A B L E 2 Arcuate expression of neuropeptides and hormone receptors in males food ingested for OPFR-exposed HFD males compared with controls in the BioDAQ, as OPFRs are known to interact with PPARγ (Pillai et al, 2014).…”

Section: Discussionmentioning

confidence: 94%

Maternal organophosphate flame‐retardant exposure alters offspring feeding, locomotor and exploratory behaviors in a sexually‐dimorphic manner in mice

Walley

Krumm

Yasrebi

et al. 2020

J of Applied Toxicology

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Increased usage of organophosphate flame retardants (OPFRs) has led to detectable levels in pregnant women and neonates, which is associated with negative neurological outcomes. Therefore, we investigated if maternal OPFR exposure altered adult offspring feeding, locomotor, and anxiety‐like behaviors on a low‐fat (LFD) or high‐fat diet (HFD). Wild‐type C57Bl/6J dams were orally dosed with vehicle (sesame oil) or an OPFR mixture (1 mg/kg combination each of tris(1,3‐dichloro‐2‐propyl)phosphate, triphenyl phosphate and tricresyl phosphate) from gestation day 7 to postnatal day 14. After weaning, pups were fed either a LFD or HFD until 19 weeks of age. Locomotor and anxiety‐like behaviors were evaluated with the open field test, elevated plus maze, and metabolic cages. Feeding behaviors and meal patterns were analyzed by a Biological Data Acquisition System. Anogenital distance was reduced in OPFR‐exposed male pups, but no effect was detected on adult body weight. We observed interactions of OPFR exposure and HFD consumption on locomotor and anxiety‐like behavior in males, suggesting an anxiogenic effect while reducing overall nighttime activity. We also observed an interaction of OPFR exposure and HFD on weekly food intake and feeding behaviors. OPFR‐exposed males consumed more total HFD than oil‐exposed males during the 72‐hour trial. However, when arcuate gene expression was analyzed, OPFR exposure induced Agrp expression in females, which would suggest greater orexigenic tone. Collectively, the implications of our study are that the behavioral effects of OPFR exposure are modulated by adult HFD consumption, which may influence the metabolic and neurological consequences of maternal OPFR exposure.

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Section: Discussionmentioning

confidence: 94%

Maternal organophosphate flame‐retardant exposure alters offspring feeding, locomotor and exploratory behaviors in a sexually‐dimorphic manner in mice

Walley

Krumm

Yasrebi

et al. 2020

J of Applied Toxicology

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“…In this study, we also confirmed for that leptin modulates the expression of POMC in the mHypoA-POMC/GFP cell line which can be thus a good model for the mechanistic studies. This model has been validated in other studies [29,[38][39][40].…”

Section: Discussionmentioning

confidence: 87%

Leptin Modulates the Expression of miRNAs-Targeting POMC mRNA by the JAK2-STAT3 and PI3K-Akt Pathways

Derghal

Astier

Sicard

et al. 2019

JCM

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The central control of energy balance involves a strongly regulated neuronal network within the hypothalamus and the brainstem. In these structures, pro-opiomelanocortin (POMC) neurons are known to decrease food intake and to increase energy expenditure. Thus, leptin, a peripheral signal that relays information regarding body fat content, modulates the activity of POMC neurons. MicroRNAs (miRNAs) are short non-coding RNAs of 22–26 nucleotides that post-transcriptionally interfere with target gene expression by binding to their mRNAs. It has been demonstrated that leptin is able to modulate the expression of miRNAs (miR-383, miR-384-3p, and miR-488) that potentially target POMC mRNA. However, no study has identified the transduction pathways involved in this effect of leptin on miRNA expression. In addition, miRNAs targeting POMC mRNAs are not clearly identified. In this work, using in vitro models, we have identified and confirmed that miR-383, miR-384-3p, and miR-488 physically binds to the 3′ untranslated (3′UTR) regions of POMC mRNA. Importantly, we show that leptin inhibits these miRNAs expression by different transduction pathways. Taken together, these results allowed us to highlight the miRNA involvement in the regulation of POMC expression downstream of the leptin signaling and satiety signal integration.

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“…To determine the effect of BPA on Pnx gene expression, mRNA levels were measured after 2, 4, 8, 16 and 24 h of 100 μM BPA treatment (Figure 3A ). This dosage has been previously found to be effective in our cell lines with the modulation of pro-opiomelanocortin (POMC) and therefore was used here ( Salehi et al, 2018 ). In the mHypoE-46 embryonic male-derived cell line, Pnx expression was downregulated at 16 h. Pnx expression was also decreased at 16 and 24 h in the adult male-derived mHypoA-2/12 cell line.…”

Section: Resultsmentioning

confidence: 99%

Phoenixin Expression Is Regulated by the Fatty Acids Palmitate, Docosahexaenoic Acid and Oleate, and the Endocrine Disrupting Chemical Bisphenol A in Immortalized Hypothalamic Neurons

2018

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Phoenixin (PNX) is a newly identified reproductive peptide required for the estrous cycle. It is most highly expressed in the hypothalamus, where it is a positive regulator of gonadotropin-releasing hormone (GnRH) and kisspeptin. However, it is unknown what signals lie upstream of Pnx to coordinate its effects on GnRH and kisspeptin. We investigated the effects of the hormones, estrogen and leptin; the fatty acids, palmitate, docosahexaenoic acid (DHA), oleate and palmitoleate; and the endocrine disrupting chemical BPA on Pnx mRNA levels. We also examined whether the signaling pathways of nitric oxide, lipopolysaccharide, cAMP and protein kinase C could alter Pnx expression. Immortalized hypothalamic neurons were treated from 2 to 24 h with these compounds and Pnx mRNA levels were measured with RT-qPCR. Unexpectedly, only BPA as well as the fatty acids, palmitate, DHA and oleate, could alter Pnx expression; therefore suggesting that Pnx may fulfill a nutrient-sensing role in the hypothalamus. Our study is the first to delineate potential regulators of this novel neuropeptide, and our findings provide some insight into the functional role of PNX in the hypothalamus.

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Bisphenol A induces Pomc gene expression through neuroinflammatory and PPARγ nuclear receptor-mediated mechanisms in POMC-expressing hypothalamic neuronal models

Cited by 23 publications

References 53 publications

Maternal organophosphate flame‐retardant exposure alters offspring feeding, locomotor and exploratory behaviors in a sexually‐dimorphic manner in mice

Maternal organophosphate flame‐retardant exposure alters offspring feeding, locomotor and exploratory behaviors in a sexually‐dimorphic manner in mice

Leptin Modulates the Expression of miRNAs-Targeting POMC mRNA by the JAK2-STAT3 and PI3K-Akt Pathways

Phoenixin Expression Is Regulated by the Fatty Acids Palmitate, Docosahexaenoic Acid and Oleate, and the Endocrine Disrupting Chemical Bisphenol A in Immortalized Hypothalamic Neurons

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