Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa-CONICET, 3000, Santa Fe, Argentina.
Instituto de Salud y Ambiente del Litoral (ISAL), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa-CONICET, 3000, Santa Fe, Argentina; Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, 3000, Santa Fe, Argentina.
Mol Cell Endocrinol. 2021 Feb 15;522:111123. doi: 10.1016/j.mce.2020.111123. Epub 2020 Dec 15.
A small litter (SL) model was used to determine how neonatal overfeeding affects the homeostatic control of food intake in male rats at weaning and postnatal day (PND) 90. At PND4, litters were reduced to small (4 pups/dam) or normal (10 pups/dam) litters. At weaning, SL rats showed higher body weight and characteristic features of the metabolic syndrome. Gene expression of pro-opiomelanocortin (POMC), cocaine and amphetamine regulated transcript, neuropeptide Y (NPY) and leptin and ghrelin (GHSR) receptors were increased and POMC promoter was hypomethylated in arcuate nucleus, indicating that the early development of obesity may involve the GHSR/NPY system and changes in POMC methylation state. At PND90, body weight, metabolic parameters and gene expression were restored; however, POMC methylation state remained altered. This work provides insight into the effects of neonatal overfeeding, showing the importance of developmental plasticity in restoring early changes in central pathways involved in metabolic programming.
采用小窝仔（SL）模型，研究了新生期过度喂养如何影响雄性大鼠断奶后和出生后第 90 天（PND90）的摄食稳态控制。在 PND4 时，将窝仔数减少到小窝仔（4 只/窝）或正常窝仔（10 只/窝）。断奶时，SL 大鼠表现出更高的体重和代谢综合征的特征。弓状核中前阿黑皮素原（POMC）、可卡因和安非他命调节转录物、神经肽 Y（NPY）和瘦素和 ghrelin（GHSR）受体的基因表达增加，POMC 启动子低甲基化，表明肥胖的早期发展可能涉及 GHSR/NPY 系统和 POMC 甲基化状态的变化。在 PND90 时，体重、代谢参数和基因表达得到恢复；然而，POMC 甲基化状态仍然发生改变。这项工作深入了解了新生期过度喂养的影响，显示了发育可塑性在恢复代谢编程中涉及的中枢途径早期变化方面的重要性。
