Alternate-day fasting delays pubertal development in normal-weight mice but prevents high-fat diet-induced obesity and precocious puberty

BACKGROUND/OBJECTIVES: Childhood obesity, particularly in girls, is linked to early puberty onset, increasing risks for adult-onset diseases. There is a need for safe, lifestyle-based strategies to manage childhood obesity and precocious puberty. This study investigates alternate-day fasting (ADF) on pubertal development in normal-weight and high-fat diet (HFD)-induced obese female mice. METHODS: Dams were maintained on control chow pre/during pregnancy, then post-parturition remained on chow or switched to HFD; offspring mirrored maternal diets. One chow and one HFD group were subjected to ADF. Morphometry and hormone analyses were performed at defined postnatal days. RESULTS: In normal-weight mice, ADF reduced body length/weight, uterine and ovarian weights, delayed puberty, and lowered sex hormones and growth hormone (GH). GH treatment rescued ADF-induced growth reduction but did not prevent delayed puberty. HFD increased body length, induced obesity and precocious puberty, and altered sex hormones and leptin; these changes were counteracted by ADF (particularly 24 h ADF). CONCLUSIONS: ADF reduced GH and sex hormone levels, contributing to reduced growth and delayed puberty in normal-weight mice. Parents of normal-weight children should be cautious about prolonged overnight fasting. ADF prevented HFD-induced obesity and precocious puberty, suggesting a potential non-invasive alternative warranting further study for clinical translation.

Rahim Ullah, Chuqing Xue, Senjie Wang, Zhewen Qin, Naveed Rauf, Shumin Zhan, Naimat Ullah Khan, Yi Shen, Yu-Dong Zhou, Junfen Fu