Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Department of Obstetrics and Gynecology, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing, China.
Biol Reprod. 2023 Apr 11;108(4):597-610. doi: 10.1093/biolre/ioad004.
Polycystic ovary syndrome (PCOS) is one of the most common female reproductive and metabolic disorders. The ketogenic diet (KD) is a diet high in fat and low in carbohydrate. The beneficial effects of KD intervention have been demonstrated in obese women with PCOS. The underlying mechanisms, however, remain unknown. The aim of the present study was to investigate the effects of a KD on both reproductive and metabolic phenotypes of dehydroepiandrosterone (DHEA)-induced PCOS mice. Female C57BL/6 mice were divided into three groups, designated Control, DHEA, and DHEA+KD groups. Mice of both Control and DHEA groups were fed the control diet, whereas DHEA+KD mice were fed a KD with 89%(kcal) fat for 1 or 3 weeks after PCOS mouse model was completed. At the end of the experiment, both reproductive and metabolic characteristics were assessed. Our data show that KD treatment significantly increased blood ketone levels, reduced body weight and random and fasting blood glucose levels in DHEA+KD mice compared with DHEA mice. Glucose tolerance, however, was impaired in DHEA+KD mice. Ovarian functions were improved in some DHEAmice after KD feeding, especially in mice treated with KD for 3 weeks. In addition, inflammation and cell apoptosis were inhibited in the ovaries of DHEA+KD mice. Results from in vitro experiments showed that the main ketone body β-hydroxybutyrate reduced inflammation and cell apoptosis in DHEA-treated KGN cells. These findings support the therapeutic effects of KD and reveal a possible mechanism by which KD improves ovarian functions in PCOS mice.
多囊卵巢综合征（PCOS）是最常见的女性生殖和代谢紊乱之一。生酮饮食（KD）是一种高脂肪、低碳水化合物的饮食。KD 干预对多囊卵巢综合征肥胖女性的有益作用已得到证实。然而，其潜在机制尚不清楚。本研究旨在探讨 KD 对脱氢表雄酮（DHEA）诱导的多囊卵巢综合征小鼠生殖和代谢表型的影响。将雌性 C57BL/6 小鼠分为三组，分别为对照组、DHEA 组和 DHEA+KD 组。对照组和 DHEA 组的小鼠均喂食对照饮食，而 DHEA+KD 组的小鼠在完成多囊卵巢综合征小鼠模型后，喂食含 89%（热量）脂肪的 KD 饮食 1 或 3 周。实验结束时，评估了生殖和代谢特征。我们的数据表明，与 DHEA 组相比，KD 治疗可显著增加 DHEA+KD 小鼠的血液酮体水平，降低体重和随机及空腹血糖水平。然而，DHEA+KD 小鼠的葡萄糖耐量受损。KD 喂养后，一些 DHEA 小鼠的卵巢功能得到改善，尤其是 KD 治疗 3 周的小鼠。此外，DHEA+KD 小鼠的卵巢中炎症和细胞凋亡受到抑制。体外实验结果表明，主要的酮体β-羟丁酸可减轻 DHEA 处理的 KGN 细胞的炎症和细胞凋亡。这些发现支持 KD 的治疗作用，并揭示了 KD 改善 PCOS 小鼠卵巢功能的可能机制。
