Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons
The hypothalamus is a vital regulator of energy homeostasis. Orexigenic neuropeptide Y (NPY) neurons within the hypothalamus can stimulate feeding and suppress energy expenditure, and dysregulation of these neurons may contribute to obesity. We previously reported that bisphenol A (BPA), an endocrin...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2073-4425/14/9/1773 |
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| author | Kimberly W. Y. Mak Wenyuan He Neruja Loganathan Denise D. Belsham |
| author_facet | Kimberly W. Y. Mak Wenyuan He Neruja Loganathan Denise D. Belsham |
| author_sort | Kimberly W. Y. Mak |
| collection | DOAJ |
| description | The hypothalamus is a vital regulator of energy homeostasis. Orexigenic neuropeptide Y (NPY) neurons within the hypothalamus can stimulate feeding and suppress energy expenditure, and dysregulation of these neurons may contribute to obesity. We previously reported that bisphenol A (BPA), an endocrine disruptor with obesogenic properties, alters <i>Npy</i> transcription in hypothalamic neurons by inducing oxidative stress. We hypothesized that hypothalamic microRNAs (miRNAs), a class of small non-coding RNAs, could directly regulate <i>Npy</i> gene expression by binding the 3′ untranslated region (UTR). Five predicted <i>Npy</i>-targeting miRNA candidates were uncovered through TargetScan and were detected in <i>Npy</i>-expressing hypothalamic neuronal cell models and hypothalamic neuronal primary cultures. BPA dysregulated the expression of a number of these hypothalamic miRNAs. We examined the effects of putative <i>Npy</i>-targeting miRNAs using miRNA mimics, and we found that miR-143-3p, miR-140-5p, miR-29b-1-5p, and let-7b-3p altered <i>Npy</i> expression in the murine hypothalamic cell lines. Importantly, miR-143-3p targets the mouse <i>Npy</i> 3′ UTR, as detected using a luciferase construct containing the potential 3′ UTR binding sites. Overall, this study established the first hypothalamic miRNA that directly targets the 3′ UTR of mouse <i>Npy</i>, emphasizing the involvement of miRNAs in the NPY system and providing an alternative target for control of NPY levels. |
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| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T22:43:28Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-7be3e40697214597be8b55392be2b04a2023-11-19T10:53:31ZengMDPI AGGenes2073-44252023-09-01149177310.3390/genes14091773Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic NeuronsKimberly W. Y. Mak0Wenyuan He1Neruja Loganathan2Denise D. Belsham3Department of Physiology, University of Toronto, Medical Sciences Building 3247A, 1 Kings College Circle, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, University of Toronto, Medical Sciences Building 3247A, 1 Kings College Circle, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, University of Toronto, Medical Sciences Building 3247A, 1 Kings College Circle, Toronto, ON M5S 1A8, CanadaDepartment of Physiology, University of Toronto, Medical Sciences Building 3247A, 1 Kings College Circle, Toronto, ON M5S 1A8, CanadaThe hypothalamus is a vital regulator of energy homeostasis. Orexigenic neuropeptide Y (NPY) neurons within the hypothalamus can stimulate feeding and suppress energy expenditure, and dysregulation of these neurons may contribute to obesity. We previously reported that bisphenol A (BPA), an endocrine disruptor with obesogenic properties, alters <i>Npy</i> transcription in hypothalamic neurons by inducing oxidative stress. We hypothesized that hypothalamic microRNAs (miRNAs), a class of small non-coding RNAs, could directly regulate <i>Npy</i> gene expression by binding the 3′ untranslated region (UTR). Five predicted <i>Npy</i>-targeting miRNA candidates were uncovered through TargetScan and were detected in <i>Npy</i>-expressing hypothalamic neuronal cell models and hypothalamic neuronal primary cultures. BPA dysregulated the expression of a number of these hypothalamic miRNAs. We examined the effects of putative <i>Npy</i>-targeting miRNAs using miRNA mimics, and we found that miR-143-3p, miR-140-5p, miR-29b-1-5p, and let-7b-3p altered <i>Npy</i> expression in the murine hypothalamic cell lines. Importantly, miR-143-3p targets the mouse <i>Npy</i> 3′ UTR, as detected using a luciferase construct containing the potential 3′ UTR binding sites. Overall, this study established the first hypothalamic miRNA that directly targets the 3′ UTR of mouse <i>Npy</i>, emphasizing the involvement of miRNAs in the NPY system and providing an alternative target for control of NPY levels.https://www.mdpi.com/2073-4425/14/9/1773microRNAshypothalamusneuropeptide Ybisphenol Aenergy homeostasis |
| spellingShingle | Kimberly W. Y. Mak Wenyuan He Neruja Loganathan Denise D. Belsham Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons Genes microRNAs hypothalamus neuropeptide Y bisphenol A energy homeostasis |
| title | Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons |
| title_full | Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons |
| title_fullStr | Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons |
| title_full_unstemmed | Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons |
| title_short | Bisphenol A Alters the Levels of miRNAs That Directly and/or Indirectly Target Neuropeptide Y in Murine Hypothalamic Neurons |
| title_sort | bisphenol a alters the levels of mirnas that directly and or indirectly target neuropeptide y in murine hypothalamic neurons |
| topic | microRNAs hypothalamus neuropeptide Y bisphenol A energy homeostasis |
| url | https://www.mdpi.com/2073-4425/14/9/1773 |
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