Fan Roger R, Beckham John D, Rajagopalan Kartik N
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Rev Endocrinol. 2025 Sep 22. doi: 10.1038/s41574-025-01184-y.
The response to infection is an energy-demanding process that bolsters cell division and protein synthesis to overcome a rapidly dividing and invasive pathogen. Paradoxically, anorexia, a conserved behavioural response to infection, sharply limits food intake during this period of high energy demand. Leptin, the release of which from adipocytes is coordinated with the immune response, signals to the hypothalamus to balance energy availability and expenditure with respect to various physiological processes. Congenital deficiency of leptin or its receptor in humans predisposes to infection. Moreover, low serum levels of leptin are associated with poor outcomes in sepsis. Leptin activates pro-opiomelanocortin neurons, which produce melanocortins, a family of peptide hormones that has diverse roles. The melanocortins have targets in many organ systems and their functions include suppressing inflammation and upregulating sympathetic tone. Here, we discuss what is known about leptin and melanocortin signalling in the response to infection, with evidence from preclinical research and human studies. We close by offering insights into how study of these pathways might be translated into therapies for infectious disease as well as new avenues for exploration.
对感染的反应是一个需要能量的过程，它会促进细胞分裂和蛋白质合成，以战胜快速繁殖和具有侵袭性的病原体。矛盾的是，厌食作为一种对感染的保守行为反应，在这个高能量需求时期会大幅限制食物摄入。瘦素由脂肪细胞释放，其释放与免疫反应相协调，它向下丘脑发出信号，以平衡各种生理过程中的能量供应和消耗。人类先天性瘦素或其受体缺乏易导致感染。此外，脓毒症患者血清瘦素水平低与不良预后相关。瘦素激活促阿片黑素细胞皮质素神经元，这些神经元产生黑素皮质素，这是一类具有多种作用的肽类激素。黑素皮质素在许多器官系统中有靶点，其功能包括抑制炎症和上调交感神经张力。在这里，我们结合临床前研究和人体研究的证据，讨论关于瘦素和黑素皮质素信号在感染反应中的已知情况。最后，我们深入探讨如何将这些信号通路的研究转化为传染病治疗方法以及新的探索途径。
