Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, FHU 1,000 Days for Health, Lille, 59000, France.
Int J Obes (Lond). 2022 Jun;46(6):1138-1144. doi: 10.1038/s41366-022-01093-4. Epub 2022 Feb 16.
BACKGROUND/OBJECTIVES: Alteration of the perinatal nutritional environment is an important risk factor for the development of metabolic diseases in later life. The hormone leptin plays a critical role in growth and development. Previous studies reported that postnatal overnutrition increases leptin secretion during the pre-weaning period. However, a direct link between leptin, neonatal overnutrition, and lifelong metabolic regulation has not been investigated.
We used the small litter mouse model combined with neonatal leptin antagonist injections to examine whether attenuating leptin during early life improves lifelong metabolic regulation in postnatally overnourished mice.
Postnatally overnourished mice displayed rapid weight gain during lactation and remained overweight as adults. These mice also showed increased adiposity and perturbations in glucose homeostasis in adulthood. Neonatal administration of a leptin antagonist normalized fat mass and insulin sensitivity in postnatally overnourished mice. These metabolic improvements were associated with enhanced sensitivity of hypothalamic neurons to leptin.
Early postnatal overnutrition causes metabolic alterations that can be permanently attenuated with the administration of a leptin antagonist during a restricted developmental window.
背景/目的：围产期营养环境的改变是导致生命后期代谢性疾病发生的一个重要危险因素。激素瘦素在生长发育中起着关键作用。先前的研究报道，新生儿期营养过剩会增加断奶前瘦素的分泌。然而，瘦素、新生儿期营养过剩与终生代谢调节之间的直接联系尚未被研究。
我们使用小窝鼠模型结合新生儿瘦素拮抗剂注射，来研究在生命早期减轻瘦素是否能改善新生后营养过剩小鼠的终生代谢调节。
新生后营养过剩的小鼠在哺乳期体重迅速增加，成年后仍然超重。这些小鼠在成年后还表现出脂肪量增加和葡萄糖稳态紊乱。新生儿给予瘦素拮抗剂可使新生后营养过剩的小鼠的脂肪量和胰岛素敏感性正常化。这些代谢改善与下丘脑神经元对瘦素敏感性的增强有关。
早期的新生后营养过剩会导致代谢改变，而在有限的发育窗口期内给予瘦素拮抗剂可以永久性地减轻这些改变。
