Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, and Department of Pediatrics, Universidad Autónoma de Madrid, Avenida Menéndez Pelayo, 65, 28009 Madrid, Spain.
Endocrinology. 2011 Nov;152(11):4116-26. doi: 10.1210/en.2011-1233. Epub 2011 Sep 20.
In rodents there is a rise in serum leptin levels between postnatal days (PND) 5 and 14, with this neonatal leptin surge reported to modulate the maturation of hypothalamic circuits involved in appetite regulation. We hypothesized that acute changes in neonatal leptin levels have different long-term metabolic effects depending on how and when this surge is modified. To advance the timing of the normal leptin peak, male Wistar rats were injected with leptin (sc, 3 μg/g) on PND 2. To ablate the leptin peak on PND 10, a pegylated leptin antagonist (sc, 9 μg/g) was injected. Controls received vehicle. All rats were allowed to eat ad libitum until PND 150. Increased leptin on PND 2 reduced food intake (P<0.01) after 3 months of age with no effect on body weight. Levels of total ghrelin were reduced (P<0.001) and acylated ghrelin increased (P<0.05), with no other modifications in metabolic hormones. In contrast, treatment with the leptin antagonist on PND 9 did not affect food intake but reduced body weight beginning around PND 60 (P<0.02). This was associated with a reduction in fat mass, insulin (P<0.01), and leptin (P<0.007) levels and an increase in testosterone levels (P<0.01). Hypothalamic neuropeptide Y (P<0.05) and leptin receptor (P<0.005) mRNA levels were reduced, whereas mRNA levels for uncoupling protein 2 (P<0.005) were increased in visceral fat, which may indicate an increase in energy expenditure. In conclusion, acute changes in neonatal leptin levels induce different metabolic profiles depending on how and when leptin levels are modified.
在啮齿动物中，血清瘦素水平在出生后第 5 天至 14 天之间上升，据报道，这种新生儿瘦素激增会调节参与食欲调节的下丘脑回路的成熟。我们假设，根据改变和何时改变新生儿瘦素水平的方式，急性瘦素水平变化会产生不同的长期代谢影响。为了提前正常瘦素峰值的时间，雄性 Wistar 大鼠在出生后第 2 天接受瘦素（sc，3μg/g）注射。为了在出生后第 10 天消除瘦素峰值，注射聚乙二醇化瘦素拮抗剂（sc，9μg/g）。对照组接受载体。所有大鼠均自由进食，直至出生后 150 天。出生后第 2 天增加瘦素会减少 3 个月龄后的食物摄入量（P<0.01），但对体重没有影响。总 ghrelin 水平降低（P<0.001），酰化 ghrelin 增加（P<0.05），代谢激素无其他变化。相比之下，在出生后第 9 天用瘦素拮抗剂治疗不会影响食物摄入量，但从出生后第 60 天左右开始降低体重（P<0.02）。这与脂肪量减少、胰岛素（P<0.01）和瘦素（P<0.007）水平降低以及睾酮水平升高（P<0.01）有关。下丘脑神经肽 Y（P<0.05）和瘦素受体（P<0.005）mRNA 水平降低，而内脏脂肪中解偶联蛋白 2（P<0.005）mRNA 水平升高，这可能表明能量消耗增加。总之，根据改变和何时改变瘦素水平的方式，新生儿瘦素水平的急性变化会导致不同的代谢特征。
