肥満関連の早熟性腺発達症のラットモデル確立のための高脂肪食製剤の最適化と検証

Childhood obesity is closely linked to the rising incidence of precocious puberty (PP), yet valid preclinical models of obesity-related PP remain lacking. High-fat diets (HFD) are widely used for obesity models, but the suitability of different HFD formulations for inducing PP is unknown. Female Sprague-Dawley (SD) rats were randomized to control, 45% HFD, or 60% HFD groups at postnatal day (PND) 21. Body weight and daily caloric intake were monitored; vaginal opening (VO) was recorded from PND 35. At study termination, serum levels of estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), gonadotropin-releasing hormone (GnRH), leptin, and adiponectin were measured. Ovarian histology and vaginal cytology were assessed. In vitro, GT1-7 cells were treated with recombinant mouse leptin for 24 h, and GnRH secretion was quantified. Compared to controls and the 60% HFD group, rats fed 45% HFD exhibited significantly increased body weight, earlier VO onset, and elevated weights of organs. The 45% HFD group also had higher serum E2, LH, FSH, GnRH, and leptin levels, alongside reduced adiponectin; ovarian histology showed advanced follicular development, and vaginal smears displayed estrus-stage cytology. In contrast, the 60% HFD group had no significant changes in body weight or hormonal parameters, and limited ovarian development. In vitro, leptin treatment significantly upregulated GnRH secretion in GT1-7 cells. The 45% HFD formulation is optimal for constructing a juvenile rat model of obesity-related PP, as it recapitulates key phenotypic, histological, and endocrine features of the disease.