Department of Obstetrics and Gynecology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University, No.99 Long Cheng Street, Taiyuan, 030032, People's Republic of China.
Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No.251 Yao Jia Yuan Road,Chao Yang District, Beijing, 100026, People's Republic of China.
Reprod Sci. 2022 Jan;29(1):173-183. doi: 10.1007/s43032-021-00671-7. Epub 2021 Nov 12.
Adulthood obesity, diabetes, and metabolic diseases are associated with small for gestational age (SGA) newborns. This association could be related to abnormal appetite signaling pathways in the hypothalamus. This study investigated the appetite regulation by the hypothalamus of SGA newborns by establishing an SGA rat model and culturing SGA neural progenitor cells (NPCs) in vitro. Models of SGA were established by maternal food restriction embryonic day 10 (E10). At E18, postpartum day 1 (P1), and P5, hypothalamic neural precursor cells (NPCs) of offspring were cultured in vitro. Immunofluorescence, Western blot (WB), and qRT-PCR were used to assess NPY, POMC, and FoxO1 expression levels. The effects on mRNA expression of the FoxO1-specific inhibitor AS1842856 were examined. The results indicated that compared with controls, NPY was higher, and POMC was lower at embryonic day 18 (E18), postpartum day 1 (P1), and P5. The proliferation and migration of NPCs in the third ventricle of SGA hypothalami were lower than in controls. After treatment with the FoxO1 inhibitor AS1842856, the differences in the mRNA expression of NPY and POMC between the two groups disappeared. NPY and POMC mRNA levels in the SGA group treated with AS1842856 were not significantly different compared with the control group without AS1842856 treatment. In conclusion, SGA pups showed an increase in appetite-promoting NPY and a decrease in appetite-reducing POMC, probably contributing to adulthood weight gain, obesity, and endocrine disorders.
成年期肥胖、糖尿病和代谢疾病与胎儿生长受限（SGA）新生儿有关。这种关联可能与下丘脑异常食欲信号通路有关。本研究通过建立 SGA 大鼠模型和体外培养 SGA 神经祖细胞（NPC）来研究 SGA 新生儿的食欲调节。通过限制母鼠饮食在胚胎第 10 天（E10）建立 SGA 模型。在产后第 1 天（P1）和第 5 天（P5），培养后代下丘脑神经前体细胞（NPC）体外。免疫荧光、Western blot（WB）和 qRT-PCR 用于评估 NPY、POMC 和 FoxO1 的表达水平。检查 FoxO1 特异性抑制剂 AS1842856 对 mRNA 表达的影响。结果表明，与对照组相比，E18、P1 和 P5 时 NPY 升高，POMC 降低。SGA 下丘脑第三脑室 NPC 的增殖和迁移低于对照组。用 FoxO1 抑制剂 AS1842856 处理后，两组之间 NPY 和 POMC 的 mRNA 表达差异消失。与未用 AS1842856 处理的对照组相比，用 AS1842856 处理的 SGA 组 NPY 和 POMC 的 mRNA 水平没有显著差异。总之，SGA 幼仔表现出食欲促进 NPY 的增加和食欲抑制 POMC 的减少，这可能导致成年期体重增加、肥胖和内分泌紊乱。
