Obesity is a chronic disease caused by excessive fat accumulation that impacts the body and brain health. Insufficient leptin or leptin receptor (LepR) are involved in the disease pathogenesis. Leptin is involved with several neurological processes, and it has critical developmental roles. We have previously demonstrated that leptin deficiency in early life leads to permanent developmental problems, including energy homeostasis imbalance, melanocortin and reproductive system alterations and brain mass reduction in young adult mice. Since in humans, obesity has been associated with brain atrophy and cognitive impairment, it is important to determine the long-term consequences of early life leptin deficiency in brain structure and memory function. Here, we demonstrate that leptin-deficient mice (LepOb) exhibit altered brain volume, decreased neurogenesis and memory impairment. Similar effects were observed in animals that do not express the LepR (LepRNull). Interestingly, restoring the expression of LepR in 10-week-old mice reverses brain atrophy, as well as neurogenesis and memory impairments in older animals. Our findings indicate that leptin deficiency impairs brain development and memory, which are reversible by restoring leptin signaling in adulthood.

中文翻译：

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瘦素受体重新激活可恢复早期 Lepr 缺陷小鼠的大脑功能

肥胖是一种由过度脂肪堆积引起的慢性疾病，影响身体和大脑健康。瘦素或瘦素受体（LepR）不足参与了疾病的发病机制。瘦素参与多种神经过程，并且具有关键的发育作用。我们之前已经证明，生命早期瘦素缺乏会导致永久性发育问题，包括能量稳态失衡、黑皮质素和生殖系统改变以及年轻成年小鼠的脑质量减少。由于在人类中，肥胖与脑萎缩和认知障碍有关，因此确定生命早期瘦素缺乏对大脑结构和记忆功能的长期影响非常重要。在这里，我们证明瘦素缺陷小鼠（LepOb）表现出脑容量改变、神经发生减少和记忆障碍。在不表达 LepR (LepRNull) 的动物中也观察到了类似的效果。有趣的是，在 10 周大的小鼠中恢复 LepR 的表达可以逆转脑萎缩，以及老年动物的神经发生和记忆障碍。我们的研究结果表明，瘦素缺乏会损害大脑发育和记忆，这可以通过在成年后恢复瘦素信号传导来逆转。