First Author | Hua L | Year | 2020 |
Journal | Clin Transl Med | Volume | 10 |
Issue | 6 | Pages | e195 |
PubMed ID | 33135359 | Mgi Jnum | J:307627 |
Mgi Id | MGI:6721239 | Doi | 10.1002/ctm2.195 |
Citation | Hua L, et al. (2020) Time-restricted feeding improves the reproductive function of female mice via liver fibroblast growth factor 21. Clin Transl Med 10(6):e195 |
abstractText | BACKGROUND: 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. METHODS: 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. RESULTS: 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 (ERK1/2 ) pathway. CONCLUSIONS: 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. |