Mao Liwei, Wang Lian, Huang Zhihai, Chen Jian-Kang, Tucker Lorelei, Zhang Quanguang
Department of Neurology, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA 30912, USA.
Department of Neurology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103, USA.
J Adv Res. 2025 Apr 1. doi: 10.1016/j.jare.2025.03.046.
Anorexia is a complex eating disorder influenced by genetic, environmental, psychological, and socio-cultural factors. Research into its molecular mechanisms and neural circuits has deepened our understanding of its pathogenesis. Recent advances in neuroscience, molecular biology, and genetics have revealed key molecular and neural circuit mechanisms underlying anorexia.
Clarify the peripheral and central molecular mechanisms regulating various types of anorexia, identify key cytokines and neural circuits, and propose new strategies for its treatment. Key scientific concepts of review: Anorexia animal models, including activity-induced, genetic mutation, and inflammation-induced types, are explored for their relevance to studying the disorder. Anorexic behavior is regulated by cytokines, hormones (like GDF15, GLP-1, and leptin), and neural circuits such as AgRP, serotonergic, dopaminergic, and glutamatergic pathways. Disruptions in these pathways, including GABAergic signaling in AgRP neurons and 5-HT2C and D2 receptors, contribute to anorexia. Potential therapies target neurotransmitter receptors, ghrelin receptors, and the GDF15-GFRAL pathway, offering insights for treating anorexia, immune responses, and obesity.
厌食症是一种受遗传、环境、心理和社会文化因素影响的复杂饮食失调症。对其分子机制和神经回路的研究加深了我们对其发病机制的理解。神经科学、分子生物学和遗传学的最新进展揭示了厌食症背后的关键分子和神经回路机制。
阐明调节各类厌食症的外周和中枢分子机制，确定关键细胞因子和神经回路，并提出新的治疗策略。综述的关键科学概念：探讨了厌食症动物模型，包括活动诱导型、基因突变型和炎症诱导型，以研究它们与该疾病的相关性。厌食行为受细胞因子、激素（如生长分化因子15、胰高血糖素样肽-1和瘦素）以及神经回路（如下丘脑弓状核AgRP、5-羟色胺能、多巴胺能和谷氨酸能通路）的调节。这些通路的破坏，包括AgRP神经元中的γ-氨基丁酸能信号以及5-羟色胺2C和多巴胺2受体，会导致厌食症。潜在的治疗方法针对神经递质受体、胃饥饿素受体以及生长分化因子15-生长分化因子受体α样蛋白（GDF15-GFRAL）通路，为治疗厌食症、免疫反应和肥胖症提供了思路。
