Hua Lun, Feng Bin, Huang Liansu, Li Jing, Luo Ting, Jiang Xuemei, Han Xingfa, Che Lianqiang, Xu Shengyu, Lin Yan, Fang Zhengfeng, Wu De, Zhuo Yong
Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, P. R. China.
Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Sichuan Agricultural University, Chengdu, P. R. China.
Clin Transl Med. 2020 Oct;10(6):e195. doi: 10.1002/ctm2.195.
There has been a significant increase, to epidemic levels, of obese and overweight women of reproductive age, causing impairments to reproductive health. Time-restricted feeding (TRF) including isocaloric intake has shown to be preventive of obesity-related disorders. However, its therapeutic ability to improve the reproductive function of female remains largely unknown.
Here, we investigated the ability of TRF to improve the reproductive function in wild-type and liver-specific FGF21 knockout female mice. To study fertility, a continuous and a short-term fertility test, gonadotropin releasing-hormone (GnRH), and Kisspeptin test were performed. Immortalized GnRH neuron was used to examine the direct role of liver fibroblast growth factor 21 (FGF21) on GnRH secretion.
We found that TRF rescues female mice from bodyweight gain and glucose intolerance, as well as ovarian follicle loss and dysfunction of estrus cyclicity induced by high-fat diet. Furthermore, the beneficial effects of the TRF regimen on the reproductive performance were also observed in mice fed both chow and high-fat diet. However, those beneficial effects of TRF on metabolism and reproduction were absent in liver-specific FGF21 knockout mice. In vitro, FGF21 directly acted on GnRH neurons to modulate GnRH secretion via extracellular regulated protein kinases (ERK ) pathway.
Overall, time-restricted feeding improves the reproductive function of female mice and liver FGF21 signaling plays a key role in GnRH neuron activity in female mice.
育龄期肥胖和超重女性的数量已大幅增加至流行水平，对生殖健康造成损害。包括等热量摄入的限时进食（TRF）已被证明可预防肥胖相关疾病。然而，其改善女性生殖功能的治疗能力在很大程度上仍不清楚。
在此，我们研究了TRF改善野生型和肝脏特异性FGF21基因敲除雌性小鼠生殖功能的能力。为了研究生育能力，进行了连续和短期生育力测试、促性腺激素释放激素（GnRH）和亲吻素测试。使用永生化GnRH神经元来研究肝脏成纤维细胞生长因子21（FGF21）对GnRH分泌的直接作用。
我们发现，TRF可使雌性小鼠免于体重增加和葡萄糖不耐受，以及高脂饮食诱导的卵巢卵泡丢失和发情周期功能障碍。此外，在喂食普通饲料和高脂饮食的小鼠中也观察到了TRF方案对生殖性能的有益影响。然而，在肝脏特异性FGF21基因敲除小鼠中，TRF对代谢和生殖的这些有益作用并不存在。在体外，FGF21通过细胞外调节蛋白激酶（ERK）途径直接作用于GnRH神经元以调节GnRH分泌。
总体而言，限时进食可改善雌性小鼠的生殖功能，肝脏FGF21信号通路在雌性小鼠GnRH神经元活性中起关键作用。
