Childhood obesity and precocious puberty are significant global health concerns, often linked and posing increased risks for various adult-onset diseases. Current medical interventions can be expensive and invasive, highlighting the need for safe and effective lifestyle-based alternatives. This study focuses on alternate-day fasting (ADF), a dietary regimen previously shown to impact the hypothalamic-pituitary-gonadal axis and body weight in other studies. The researchers hypothesize that ADF could be an effective strategy for managing both childhood obesity and precocious puberty by modulating hormonal levels and growth.

The introduction extensively cites existing literature on the prevalence and health consequences of childhood obesity and precocious puberty, particularly in the Chinese population. It also reviews the established links between these conditions, as well as the limitations of current medical treatments. Several studies on intermittent fasting and its impact on body weight and metabolic parameters are mentioned, establishing a foundation for the investigation of ADF's potential as a therapeutic strategy.

The study utilized four groups of female C57BL/6J mice: a control group fed standard chow, an HFD group fed a high-fat diet, and ADF versions of each group. Dams were fed control chow before and during pregnancy; after birth, two groups continued on control chow and two switched to an HFD, with the offspring mimicking their mothers' diet. One control group and one HFD group were subjected to ADF (18 hours or 24 hours), beginning after weaning. Body weight, length, puberty onset (vaginal opening), and various hormone levels (LH, FSH, estradiol, insulin, leptin, GH, IGF-1) were measured at various time points (P34 and P40 for the control and 18h ADF groups, P34 for others). A separate experiment was conducted to examine the effect of rhGH treatment on ADF-induced growth reduction in normal-weight mice. Detailed statistical analyses were performed to compare groups.

In normal-weight mice, 18h ADF delayed puberty onset (significantly later vaginal opening), reduced body weight and length, and lowered uterine and ovarian weights. Plasma levels of FSH and estradiol were significantly reduced at P34. Growth hormone (GH) levels were lower at P34 but increased at P40 in the ADF group. In HFD-fed mice, 18h ADF prevented HFD-induced increases in body weight and length but did not prevent precocious puberty. However, 24h ADF completely prevented both the obesity and the precocious puberty, and also normalized levels of FSH and estradiol. Importantly, GH treatment in ADF normal-weight mice reversed the growth reduction but did not prevent the delay in puberty, suggesting different mechanisms for these effects. The 24h ADF group showed a significant reduction in uterine weight and leptin levels compared to the HFD group.

The results suggest that ADF's effects on pubertal development are mediated by different mechanisms in normal-weight versus obese mice. In normal-weight mice, the reduced levels of sex hormones (FSH and estradiol), likely due to the ADF regimen, are implicated in delaying puberty. The reduced GH and IGF-1 levels contribute to the growth retardation, while leptin levels remain unaffected. However, in HFD-induced obese mice, elevated leptin levels are a critical factor driving precocious puberty. The 24h ADF regimen successfully normalizes leptin levels and reverses the effects of the HFD on reproductive hormone levels, preventing precocious puberty. The authors suggest that longer periods of fasting might be more effective in altering leptin levels and preventing precocious puberty in obese mice.

Alternate-day fasting (ADF) shows promise as a potential intervention for childhood obesity and precocious puberty. While 18h ADF is effective in counteracting HFD-induced growth acceleration, 24h ADF is necessary to prevent precocious puberty in obese mice. However, in normal-weight mice, 18h ADF leads to delayed puberty and reduced growth. The results highlight the complex interplay between nutritional status, hormonal regulation, and pubertal development. Further research, including clinical trials, is crucial to determine the safety and efficacy of ADF as a therapeutic strategy in humans.

The study is conducted on mice, and the results may not directly translate to humans. The long-term effects of ADF on reproductive health and overall health are not fully explored in this study. The study primarily focuses on female mice; further research is needed to investigate the effects in male mice. The specific mechanisms underlying ADF's effects require further investigation. The observed differences between 18h and 24h ADF require further elucidation.