Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, and the National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Eur J Immunol. 2019 Jan;49(1):19-29. doi: 10.1002/eji.201747389. Epub 2018 Nov 16.
The involvement of macrophages in the pathogenesis of obesity has been recognized since 2003. Early studies mostly focused on the role of macrophages in adipose tissue (AT) and in obesity-associated chronic low-grade inflammation. Lately, AT macrophages were shown to undergo intrinsic metabolic changes that affect their immune function (i.e., immunometabolism), corresponding to their unique properties along the range of pro- versus anti-inflammatory activity. In parallel, recent studies in mice revealed critical neuronal-macrophage interactions, both in the CNS and in peripheral tissues, including in white and brown AT. These intercellular activities impinge on energy and metabolic homeostasis, partially by also engaging adipocytes in a neuronal-macrophage-adipocyte ménage à trois. Finally, neuropeptides (NP), such as NPY and appetite-reducing NPFF, may prove as mediators in such intercellular network. In this concise review, we highlight some of these recent insights on adipose macrophage immunometabolism, as well as central and peripheral neuronal-macrophage interactions with emphasis on their impact on adipocyte biology and whole-body metabolism. We also discuss the expanding view on the role of the NP, NPY and NPFF, in obesity.
自 2003 年以来，人们已经认识到巨噬细胞在肥胖发病机制中的作用。早期的研究主要集中在巨噬细胞在脂肪组织（AT）和肥胖相关的慢性低度炎症中的作用。最近，研究表明 AT 巨噬细胞发生内在的代谢变化，影响其免疫功能（即免疫代谢），这与它们沿着促炎与抗炎活动范围的独特特性相对应。与此同时，最近在小鼠中的研究揭示了中枢神经系统和外周组织中（包括白色和棕色 AT）关键的神经元-巨噬细胞相互作用。这些细胞间的活动影响能量和代谢稳态，部分原因是还使脂肪细胞参与神经元-巨噬细胞-脂肪细胞三人组。最后，神经肽（NP），如 NPY 和食欲抑制性 NPFF，可能被证明是这种细胞间网络的介质。在这篇简明的综述中，我们强调了一些关于脂肪巨噬细胞免疫代谢的最新见解，以及中枢和外周神经元-巨噬细胞相互作用，重点是它们对脂肪细胞生物学和全身代谢的影响。我们还讨论了对 NP、NPY 和 NPFF 在肥胖中的作用的扩展观点。
