High-fat diet-induced obesity accelerates puberty in male rats through SMIM20/phoenixin upregulation.
Xie. Tao T; Qin. Wei W; Zeng. Dan D; Wang. Runqi R; Chen. Shuting S; Chen. Yanfei Y; Zhong. Jingzi J; Lan. Dan D
Key Findings
- High‑fat diet caused obesity and earlier preputial separation (a sign of puberty) in male rats.
- Obese rats showed higher expression of GnRH, Kiss1, GPR54, GnRH receptor and increased serum LH, FSH, and testosterone.
- Phoenixin (PNX) levels and Smim20 expression were significantly higher in the hypothalamus, pituitary, testes, and fat of obese rats.
Practical Outcomes
- For biohackers, the main takeaway is that excess body fat may accelerate male puberty via hormonal pathways, highlighting a potential downside of chronic over‑nutrition. While phoenixin emerges as a possible molecular link, the research does not provide a usable protocol, dosage, or direct intervention for humans.
Summary
Feeding young male rats a high‑fat diet made them fatter and caused them to hit puberty earlier. The extra fat also boosted hormones that control reproduction and raised levels of a brain peptide called phoenixin (produced from the Smim20 gene). The study suggests that obesity can speed up puberty in males, possibly through phoenixin, but it was done in rats and does not give a clear way to use this information in humans.
Abstract
Controversy exists regarding the relationship between obesity and pubertal onset in boys, and the underlying mechanisms remain unclear. To establish a high-fat diet (HFD)-induced obesity model in juvenile male Sprague-Dawley (SD) rats, and to investigate the relationship between obesity and pubertal advancement as well as the role of <i>Smim20</i>/phoenixin (PNX) in male pubertal development. A HFD (45% fat) was administered to male SD rats to induce obesity, while control rats were maintained on a normal diet (ND) from birth. Body weight and preputial separation were monitored as markers of obesity and pubertal onset. At prepubertal (postnatal day 30, PND30) and early pubertal (PND40) stages, serum, hypothalamus, pituitary, testes, and adipose tissue were collected. RT-qPCR was performed to measure the mRNA expression levels of key genes in the hypothalamic-pituitary-gonadal axis (HPGA), including gonadotropin-releasing hormone (<i>GnRH</i>), <i>Kiss1</i>, G protein-coupled receptor 54 (<i>GPR54</i>), GnRH receptor (<i>GnRHr</i>), and <i>Smim20</i>. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and PNX protein were measured by ELISA. Associations among obesity (body mass index, BMI), PNX, and pubertal timing were evaluated using Spearman's correlation. HFD-fed rats exhibited significantly greater body weight and fat mass than ND-fed rats at both time points. (P<0.001), with earlier preputial separation (P<0.001). Testicular weight and expression of <i>GnRH, Kiss1, GPR54, and GnRH</i>r were increased, alongside higher serum LH, FSH, and testosterone (all P<0.05). PNX expression in hypothalamus, pituitary, testes, and subcutaneous fat, as well as serum PNX-14 and PNX-20 levels, were significantly elevated in HFD rats compared with controls (P<0.05). After adjusting for BMI, serum PNX-20 and PNX-14 (P<0.001) remained higher in the HFD group. Body weight was negatively correlated with age at preputial separation and positively correlated with serum LH, testosterone, abdominal circumference, PNX. To our knowledge, this study established a novel HFD-induced model of prepubertal obesity and central precocious puberty (CPP) in male rats. The findings suggest that obesity may accelerate pubertal onset, and that Smim20/PNX may participate in regulating pubertal development in males.
Study Information
pubmed
2025
2025-11-21T00:00:00.000Z
10.3389/fendo.2025.1711374
47