Department of Clinical Haematology, Centro Hospitalar Universitário of Porto, Largo Professor Abel Salazar, 4099-001, Porto, Portugal.
Unit for Multidisciplinary Research in Biomedicine, Abel Salazar Institute of Biomedical Sciences, University of Porto- UMIB/ICBAS/UP, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313, Porto, Portugal.
J Neuroimmune Pharmacol. 2020 Mar;15(1):93-113. doi: 10.1007/s11481-019-09863-0. Epub 2019 Jul 17.
The overwhelming prevalence of obesity is a priority for public health compromising human lifespan and representing important economic burden worldwide. Obesity is characterized by a state of chronic low-grade inflammation associated to metabolic dysfunction. Although the efforts for unravelling the complex immunometabolic signaling pathways to explain the association of obesity with type 2 diabetes, cardiovascular diseases, cancer, neurodegenerative diseases and psychiatric disorders, we still do not have all the picture to design effective therapeutic to fight these immunometabolic disease clusters. Dopaminergic pathways apart from having a major role in the regulation of appetite and feeding behaviors are important immunoregulators in inflammation; thus, dopaminergic regulation is suggested to impact obesity- associated inflammation. Dopamine (DA) has been reported to modulate immune function and immune cells themselves produce endogenous DA. DA-induced immunomodulation is currently the focus of intense experimental research and dopaminergic pathways are increasingly considered a target for drug development in immune diseases. While the role of dopaminergic pathways in immune-mediated diseases has been intensively investigated in neurodegenerative diseases, dopaminergic immunomodulation in obesity-associated inflammation is largely unknown. This review will integrate the actual knowledge about dopaminergic pathways involved in obesity-associated inflammation with special focus on immune innate key cell players. We present an explanatory hypothesis with a model that integrate central and peripheral dopaminergic circuits in the relationship between neuroimmune and metabolic systems in obesity-associated inflammation. A perspective on the potential role of dopaminergic drugs in the context of obesity will be given. Graphical Abstract Graphical representation of central and peripheral dopaminergic pathways in obesity-associated inflammation.
肥胖症的广泛流行是公共卫生的重点，它缩短了人类的寿命，并在全球范围内造成了巨大的经济负担。肥胖症的特征是一种慢性低度炎症状态，与代谢功能障碍有关。尽管人们努力揭示复杂的免疫代谢信号通路，以解释肥胖与 2 型糖尿病、心血管疾病、癌症、神经退行性疾病和精神障碍之间的关联，但我们仍然无法全面了解这些疾病，无法设计出有效的治疗方法来对抗这些免疫代谢疾病。除了在调节食欲和进食行为方面发挥主要作用外，多巴胺能通路还是炎症中的重要免疫调节剂；因此，多巴胺能调节被认为会影响与肥胖相关的炎症。已经有报道称，多巴胺 (DA) 可以调节免疫功能，而免疫细胞本身也会产生内源性 DA。DA 诱导的免疫调节目前是实验研究的重点，多巴胺能通路在免疫疾病的药物开发中越来越受到关注。虽然在神经退行性疾病中，已经深入研究了多巴胺能通路在免疫介导疾病中的作用，但在肥胖相关炎症中，多巴胺能免疫调节的作用在很大程度上仍是未知的。本文将整合与肥胖相关炎症中涉及的多巴胺能通路相关的现有知识，特别关注免疫先天关键细胞因子。我们提出了一个解释性假说，该假说整合了肥胖相关炎症中神经免疫和代谢系统之间的中枢和外周多巴胺能回路。本文还将从肥胖症的角度探讨多巴胺能药物的潜在作用。
