Impact of prepubertal obesity induced by high-fat diet during lactation and post-weaning on puberty initiation and neuroendocrine function in a female mouse model.

To explore the effects of prepubertal obesity induced by high-fat diet during lactation and post-weaning on puberty onset and the neuroendocrine changes before puberty onset in a female mouse model, which may explain obesity in children starting early puberty.A total of 72 female mice were assigned to the high fat diet group (HFD) and the control diet group (CONT) during lactation and post-weaning. The bodily indexes; pathological changes; and protein and gene expression levels in the hypothalamus were examined on postnatal days (P) 15, 28, and 45, respectively.The average vaginal opening time in HFD mice occurred significantly earlier than that in CONT mice (p < 0.05). On P15, no significant difference in the MKRN3, kisspeptin, GPR54 and GnRH level between HFD and CONT mice was noted (p > 0.05). Whereas on P28 and 45, compared to CONT mice, GnRH expression in HFD mice was significantly increased (p < 0.05); kisspeptin and GPR54 expression in HFD mice was also significantly increased (p < 0.05); but the MKRN3 level in HFD mice was significantly lower than that in CONT mice (p < 0.05). On P15, 28, and 45, compared with CONT mice, miR-30b expression in HFD mice increased (p < 0.05). Compared to P15, miR-30b, KiSS-1, GPR54 and GnRH mRNA level increased significantly, however MKRN3 decreased significantly in HFD mice on P28 and 45 (p < 0.01).Prepubertal obesity induced by high-fat diet during lactation and post-weaning may advance the time of pubertal initiation in female mice. The increased expression of miR-30b, kisspeptin, GPR54 and GnRH, decreased the expression of MKRN3 may explain the early onset of puberty in obese female mice.