한빛사논문
- 조회308
Seokjae Park 1,2, Sungjoon Oh 1,2, Nayoun Kim 1 and Eun-Kyoung Kim *,1,2
1Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea
2Neurometabolomics Research Center, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Korea
*Corresponding author: correspondence to Eun-Kyoung Kim
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.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2023-11-28)
- 국내 연구진
- 생명과학 > 신경생물학
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