1. Academic Validation
  2. FoxO1 Regulates Neuropeptide Y and Pro-opiomelanocortin in the Hypothalamus of Rat Offspring Small for Gestational Age

FoxO1 Regulates Neuropeptide Y and Pro-opiomelanocortin in the Hypothalamus of Rat Offspring Small for Gestational Age

  • Reprod Sci. 2022 Jan;29(1):173-183. doi: 10.1007/s43032-021-00671-7.
Lifang Zhang 1 Qingyun Shi 2 Yiyao Sun 3
Affiliations

Affiliations

  • 1 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.
  • 2 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. shiqingyun65@163.com.
  • 3 Department of Obstetrics and Gynecology, Yuncheng Central Hospital, Shanxi Medical University, No.3690 He Dong East Street, Yuncheng, 044000, People's Republic of China.
Abstract

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.

Keywords

FoxO1; Hypothalamus; Neural precursor cells; Neuropeptide Y; Pro-opiomelanocortin; Small for gestational age.

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