HMBA ameliorates obesity by MYH9‐ and ACTG1 ‐dependent regulation of hypothalamic neuropeptides
Abstract: The global epidemic of obesity remains a daunting problem. Here, we report hexamethylene bisacetamide (HMBA) as a potent anti‐obesity compound. Peripheral and central administration of HMBA to diet‐induced obese mice regulated the expression of hypothalamic neuropeptides critical for energy balance, leading to beneficial metabolic effects such as anorexia and weight loss. We found that HMBA bound to MYH9 and ACTG1, which were required for the anti‐obesity effects of HMBA in both NPY‐expressing and POMC‐expressing neurons. The binding of HMBA to MYH9 and ACTG1 elevated the expression of HEXIM1 and enhanced its interaction with MDM2, resulting in the dissociation of the HEXIM1–p53 complex in hypothalamic cells. Subsequently, the free HEXIM1 and p53 translocated to the nucleus, where they downregulated the transcription of orexigenic NPY, but p53 and acetylated histone 3 upregulated that of anorexigenic POMC. Our study points to a previously unappreciated efficacy of HMBA and reveals its mechanism of action in metabolic regulation, which may propose HMBA as a potential therapeutic strategy for obesity.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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HMBA ameliorates obesity by MYH9‐ and ACTG1 ‐dependent regulation of hypothalamic neuropeptides ; day:20 ; month:11 ; year:2023 ; extent:30
EMBO molecular medicine / European Molecular Biology Organization ; (20.11.2023) (gesamt 30)
- Creator
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Park, Seokjae
Oh, Sungjoon
Kim, Nayoun
Kim, Eun‐Kyoung
- DOI
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10.15252/emmm.202318024
- URN
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urn:nbn:de:101:1-2023112114135041025983
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:23 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Park, Seokjae
- Oh, Sungjoon
- Kim, Nayoun
- Kim, Eun‐Kyoung
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