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<p>Polycystic ovary syndrome (PCOS) is a prevalent reproductive and metabolic disorder frequently accompanied by obesity, creating a dual burden of infertility and metabolic disease for women, yet therapeutic options addressing both pathologies remain limited. Here, using high-fat diet-induced obese and dehydroepiandrosterone-induced PCOS mouse models, we demonstrate that alnustone, a naturally derived compound, exerts coordinated benefits on both metabolic and reproductive dysfunctions in females. Long-term alnustone administration effectively attenuated body weight gain, adipocyte hypertrophy, and insulin resistance. Critically, hyperandrogenism, estrous cycle irregularity, and polycystic ovarian morphology were concurrently reversed. Mechanistically, alnustone enhanced energy expenditure by activating brown adipose tissue (BAT) and promoting white adipose tissue browning through induction of thermogenic programs. Transcriptomic profiling further revealed that alnustone corrected lipid metabolic dysregulation in obese and PCOS mice via activating adipose tissue AMPK signaling. These findings establish alnustone as a dual-action therapeutic agent that restores both metabolic homeostasis and reproductive function through adipose tissue remodeling, highlighting its potential as a natural intervention for integrated management of obesity and PCOS.</p>

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Alnustone ameliorates obesity and polycystic ovary syndrome by remodeling adipose metabolism via AMPK signaling

  • 期刊论文

  • 发表日期：

    2026年4月28日

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  • Yiming Qin,
  • Shourui Hu,
  • Yanqi Xu,
  • Zongxuan Lin,
  • Xiaofan Liang,
  • Yue Liu,
  • Yuxuan Li,
  • Chunxuan Geng,
  • Xiangyan Chen,
  • Xizi Feng,
  • Zi-Jiang Chen,
  • Han Zhao,
  • Yuqing Zhang

摘要

Polycystic ovary syndrome (PCOS) is a prevalent reproductive and metabolic disorder frequently accompanied by obesity, creating a dual burden of infertility and metabolic disease for women, yet therapeutic options addressing both pathologies remain limited. Here, using high-fat diet-induced obese and dehydroepiandrosterone-induced PCOS mouse models, we demonstrate that alnustone, a naturally derived compound, exerts coordinated benefits on both metabolic and reproductive dysfunctions in females. Long-term alnustone administration effectively attenuated body weight gain, adipocyte hypertrophy, and insulin resistance. Critically, hyperandrogenism, estrous cycle irregularity, and polycystic ovarian morphology were concurrently reversed. Mechanistically, alnustone enhanced energy expenditure by activating brown adipose tissue (BAT) and promoting white adipose tissue browning through induction of thermogenic programs. Transcriptomic profiling further revealed that alnustone corrected lipid metabolic dysregulation in obese and PCOS mice via activating adipose tissue AMPK signaling. These findings establish alnustone as a dual-action therapeutic agent that restores both metabolic homeostasis and reproductive function through adipose tissue remodeling, highlighting its potential as a natural intervention for integrated management of obesity and PCOS.