INSERM, Centre de Recherche St-Antoine, Sorbonne Université, F-75012 Paris, France.
IHU-ICAN Institute of Cardiometabolism and Nutrition, F-75013 Paris, France.
Nutrients. 2023 Feb 21;15(5):1077. doi: 10.3390/nu15051077.
Nutrition during the early postnatal period can program the growth trajectory and adult size. Nutritionally regulated hormones are strongly suspected to be involved in this physiological regulation. Linear growth during the postnatal period is regulated by the neuroendocrine somatotropic axis, whose development is first controlled by GHRH neurons of the hypothalamus. Leptin that is secreted by adipocytes in proportion to fat mass is one of the most widely studied nutritional factors, with a programming effect in the hypothalamus. However, it remains unclear whether leptin stimulates the development of GHRH neurons directly. Using a Ghrh-eGFP mouse model, we show here that leptin can directly stimulate the axonal growth of GHRH neurons in vitro in arcuate explant cultures. Moreover, GHRH neurons in arcuate explants harvested from underfed pups were insensitive to the induction of axonal growth by leptin, whereas AgRP neurons in these explants were responsive to leptin treatment. This insensitivity was associated with altered activating capacities of the three JAK2, AKT and ERK signaling pathways. These results suggest that leptin may be a direct effector of linear growth programming by nutrition, and that the GHRH neuronal subpopulation may display a specific response to leptin in cases of underfeeding.
出生后早期的营养可以规划生长轨迹和成年体型。营养调节激素强烈怀疑参与这种生理调节。生后期间的线性生长受神经内分泌生长激素轴调节，其发育首先受下丘脑 GHRH 神经元控制。脂肪量比例分泌的瘦素是研究最多的营养因素之一，在下丘脑具有编程作用。然而，尚不清楚瘦素是否直接刺激 GHRH 神经元的发育。使用 Ghrh-eGFP 小鼠模型，我们在此表明，瘦素可以在弓状体外植体培养物中直接刺激 GHRH 神经元的轴突生长。此外，从饥饿幼仔中采集的弓状体外植体中的 GHRH 神经元对瘦素诱导的轴突生长不敏感，而这些外植体中的 AgRP 神经元对瘦素处理有反应。这种不敏感性与三种 JAK2、AKT 和 ERK 信号通路的激活能力改变有关。这些结果表明，瘦素可能是营养线性生长编程的直接效应物，而在喂养不足的情况下，GHRH 神经元亚群可能对瘦素有特定的反应。
