Progressive estrogen decline during perimenopause drives glucose and lipid metabolic disorders, raising risks for diabetes and cardiovascular disease. Current therapies like hormone replacement carry safety concerns, creating a need for precise interventions. Using aged perimenopausal mice, this study applied an isoleucine-restricted diet, which reversed weight gain, insulin resistance, hepatic steatosis, and inflammation. Its core innovation is an integrated “diet-gut microbiota-host metabolism” model: the diet enriched beneficial bacteria like Ligilactibacillus murinus, elevating SCFAs (acetate/propionate). These SCFAs repaired gut barrier integrity, inhibited NF-κB, and synergistically modulated PI3K/AKT, mTOR, and AMPK pathways to restore metabolic homeostasis. This study first confirms the diet’s value in estrogen-deficient perimenopause, breaking traditional calorie restriction limits, and provides novel targets for precise nutritional intervention, with significant theoretical and clinical transformation potential.
Gao et al. (2026) studied this question.