Integrated Multiomics Analyses Reveal Molecular Insights into How Intermittent Fasting Ameliorates Obesity and Increases Fertility in Male Mice

作者：Shuyu Zhang, Tingting Lin, Yucheng Bao, Junsen She, Xuanqi Liu, Xuanqi Liu, Jundong Hu, Aibing Peng, Xinmei Liu, Xinmei Liu, Hefeng Huang · 发表于：Nutrients · 年份：2025 · DOI：10.3390/nu17061029 · 被引用次数：3 · 研究领域：Dietary Effects on Health、Diet and metabolism studies、Cancer-related molecular mechanisms research

Background: Intermittent fasting (IF) has been increasingly recognized for its potential to mitigate obesity and diabetes. However, it remains unclear whether IF can alleviate metabolic disorder-induced male infertility. The aim of this study was to investigate the potential of IF to improve fertility outcomes in obese mice. Methods: Eight-week-old C57BL/6J mice were fed a high-fat diet (HFD) for 24 weeks to induce obesity, followed by alternate-day fasting for 6 weeks. We assessed obesity-related metabolic changes and fertility issues postintervention. Comprehensive metabolomic and transcriptomic analyses of serum and testicular samples were used to identify significant metabolic pathway modifications attributable to IF. Results: IF effectively alleviated obesity-induced male infertility, demonstrating significant attenuation of body weight gain and restoration of testicular morphology. IF normalized hypogonadism-associated testosterone depletion and improved sperm parameters. Testis multi-omics integration revealed IF-mediated reprogramming of testicular purine metabolism, coupled with coordinated regulation of glycolipid metabolism and inflammatory-immune homeostasis. Reproductive competence was enhanced as evidenced by statistically elevated successful mating rates and embryonic developmental progression. Serum metabolomics further identified metabolites involved in amino acid metabolism, glycolipid metabolism, and inflammation (e.g., methionine, BCAA, glutathione, and sp...