Tian Wen, Wang Jinghui, Zhu Yangyang, Zhang Yi, Chen Liwei, Hu Cheng
Jinzhou Medical University Graduate Training Base (Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine), Jinzhou, China.
Department of Endocrinology, Xihua Xian People's Hospital, Zhoukou, China.
Front Endocrinol (Lausanne). 2025 Mar 21;16:1544213. doi: 10.3389/fendo.2025.1544213. eCollection 2025.
Obesity has become a significant public health issue, yet its underlying mechanisms remain complex. The hypothalamus, a crucial part of the central nervous system, plays a vital role in maintaining energy balance. Disruptions in hypothalamic homeostasis can lead to obesity and related metabolic disorders. Recent studies have increasingly focused on the role of intercellular interactions within the hypothalamus in obesity development, though the exact mechanisms are still under investigation. Mast cells, as innate immune cells, have been linked to obesity, but their specific roles and mechanisms require further exploration. This study aims to investigate whether hypothalamic mast cells influence microglia and subsequently affect metabolic homeostasis.
We conducted experiments to examine the effects of high-fat diets on mast cells in the arcuate nucleus of the hypothalamus. We analyzed the activation of microglia and the activity of POMC neurons in response to mast cell activation. The study involved feeding mice a high-fat diet and then assessing changes in mast cell populations, microglial activation, and neuronal activity in the hypothalamus.
Our findings indicate that high-fat feeding increases the number of mast cells in the arcuate nucleus of the hypothalamus. These mast cells activate microglia, which in turn suppress the activity of POMC neurons. This suppression promotes appetite and reduces energy expenditure, leading to obesity. The results suggest a direct role of hypothalamic mast cells in the regulation of energy balance and obesity development.
This study highlights the regulatory role of mast cells in the hypothalamus in the formation of obesity. By activating microglia and influencing POMC neuron activity, mast cells contribute to metabolic dysregulation. These findings provide a new target for the treatment of obesity and related metabolic diseases, emphasizing the importance of hypothalamic immune interactions in metabolic health. Further research is needed to explore the potential therapeutic applications of targeting mast cells in obesity management.
肥胖已成为一个重大的公共卫生问题，但其潜在机制仍然复杂。下丘脑作为中枢神经系统的关键部分，在维持能量平衡方面起着至关重要的作用。下丘脑稳态的破坏可导致肥胖及相关代谢紊乱。最近的研究越来越关注下丘脑内细胞间相互作用在肥胖发展中的作用，尽管确切机制仍在研究中。肥大细胞作为固有免疫细胞，已被证明与肥胖有关，但其具体作用和机制需要进一步探索。本研究旨在探讨下丘脑肥大细胞是否影响小胶质细胞，进而影响代谢稳态。
我们进行了实验，以研究高脂饮食对下丘脑弓状核肥大细胞的影响。我们分析了小胶质细胞的激活以及POMC神经元对肥大细胞激活的反应活性。该研究包括给小鼠喂食高脂饮食，然后评估下丘脑肥大细胞数量、小胶质细胞激活和神经元活性的变化。
我们的研究结果表明，高脂喂养会增加下丘脑弓状核中肥大细胞的数量。这些肥大细胞激活小胶质细胞，进而抑制POMC神经元的活性。这种抑制作用会促进食欲并减少能量消耗，从而导致肥胖。结果表明下丘脑肥大细胞在能量平衡调节和肥胖发展中具有直接作用。
本研究强调了肥大细胞在下丘脑肥胖形成中的调节作用。通过激活小胶质细胞并影响POMC神经元活性，肥大细胞导致代谢失调。这些发现为肥胖及相关代谢疾病的治疗提供了新的靶点，强调了下丘脑免疫相互作用在代谢健康中的重要性。需要进一步研究以探索针对肥大细胞在肥胖管理中的潜在治疗应用。
