Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 310052, China; Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Brain Science and Brain Medicine, Hangzhou, China.
Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Brain Science and Brain Medicine, Hangzhou, China.
Metabolism. 2023 Oct;147:155677. doi: 10.1016/j.metabol.2023.155677. Epub 2023 Aug 4.
Over the past few decades, there has been a global increase in childhood obesity. This rise in childhood obesity contributes to the susceptibility of impaired metabolism during both childhood and adulthood. The hypothalamus, specifically the arcuate nucleus (ARC), houses crucial neurons involved in regulating homeostatic feeding. These neurons include proopiomelanocortin (POMC) and agouti-related peptide (AGRP) secreting neurons. They play a vital role in sensing nutrients and metabolic hormones like insulin, leptin, and ghrelin. The neurogenesis of AGRP and POMC neurons completes at birth; however, axon development and synapse formation occur during the postnatal stages in rodents. Insulin, leptin, and ghrelin are the essential regulators of POMC and AGRP neurons. Maternal obesity and postnatal overfeeding or a high-fat diet (HFD) feeding cause metabolic inflammation, disrupted signaling of metabolic hormones, netrin-1, and neurogenic factors, neonatal obesity, and defective neuronal development in animal models; however, the mechanism is unclear. Within the hypothalamus and other brain areas, there exists a wide range of interconnected neuronal populations that regulate various aspects of feeding. However, this review aims to discuss how perinatal metabolic inflammation influences the development of POMC and AGRP neurons within the hypothalamus.
在过去的几十年中，儿童肥胖症在全球范围内呈上升趋势。儿童肥胖症的增加导致儿童和成年期代谢受损的易感性增加。下丘脑，特别是弓状核（ARC），包含参与调节体内平衡喂养的关键神经元。这些神经元包括前阿黑皮素原（POMC）和刺鼠相关肽（AGRP）分泌神经元。它们在感知营养物质和代谢激素（如胰岛素、瘦素和胃饥饿素）方面发挥着重要作用。AGRP 和 POMC 神经元的神经发生在出生时完成；然而，在啮齿动物的产后阶段，轴突发育和突触形成发生。胰岛素、瘦素和胃饥饿素是 POMC 和 AGRP 神经元的重要调节因子。母体肥胖和产后过度喂养或高脂肪饮食（HFD）喂养会导致代谢炎症、代谢激素信号中断、netrin-1 和神经发生因子、新生儿肥胖以及动物模型中神经元发育缺陷；然而，其机制尚不清楚。在下丘脑和其他脑区，存在着广泛的相互连接的神经元群体，它们调节着摄食的各个方面。然而，本综述旨在讨论围产期代谢炎症如何影响下丘脑内 POMC 和 AGRP 神经元的发育。
