Time‐restricted feeding improves the reproductive function of female mice via liver fibroblast growth factor 21

Abstract

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 releasinghormone (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 (ERK 1/2) pathway. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Time-Restricted Feeding in Commercial Layer Chickens Improves Egg Quality in Old Age and Points to Lack of Adipostat Activity in Chickens

“…Time-restricted feeding (TRF), defined as food consumed for ≤10 h per day, extends the time spent fasting and improves markers of metabolic health in both animal models (Froy and Miskin, 2010;Hatori et al, 2012) and humans (Sutton et al, 2018;Jones et al, 2020). In mammals, the improved health, metabolism, reproductive efficiency, brain signaling, and longevity were reported by many studies, with caloric intake similar to the ad libitum control group (Froy and Miskin, 2010;Hatori et al, 2012;Manoogian and Panda, 2017;Balasubramanian et al, 2020;Currenti et al, 2020;Hua et al, 2020). A global "experiment" in humans is Ramadan, a Muslim observance that consists of fasting from sunrise to sunset for a month: this practice has limited or no effect on body weight (BW) or body composition while improving blood lipid profile, insulin sensitivity, and other metabolic parameters; these beneficial physiological effects usually last beyond the Ramadan period (Osman et al, 2020).…”

Beneficial effects of a decreased meal frequency on nutrient utilization, secretion of luteinizing hormones and ovarian follicular development in gilts

“…FGF21 was first discovered as a fast-response hormone [ 45 , 46 ], and was later observed to be induced by a variety of nutritional situations such as a low-protein diet [ 17 , 47 , 48 ], and a ketogenic diet [ 49 , 50 ], but not by caloric restriction [ 48 ]. In our previous research, we found that time-restricted feeding rescues female mice from body weight gain and glucose intolerance as well as from ovarian follicle loss and dysfunction of estrus cyclicity induced by a high-fat diet via liver FGF21 [ 13 ]. The different effects of MF and caloric restriction on FGF21 secretion, suggests that the beneficial effects of a lower MF are completely different from caloric restriction.…”

“…The freshly collected samples were then transported in solidified carbon dioxide and stored at − 80 °C until analysis. The SCFAs concentrations in the feces were analyzed through a gas chromatographic method as previously described [ 13 ]. Briefly, 0.7 g of fecal sample was suspended in 1.5 mL of distilled water, mixed, and allowed to stand for 30 min.…”

“…This evidence indicates that the MF might play a critical role in the female reproductive system because a body of experimental evidence indicates a fundamental link between the metabolic status and the normal estrus cycle [ 3 – 5 ]. In our previous research, time-restricted feeding rescues female mice from body weight gain and glucose intolerance, as well as from the ovarian follicle loss and dysfunction of estrus cyclicity induced by a high-fat diet [ 13 ]. However, there is currently no clear evidence showing the effect of MF on the HPG axis in gilts.…”

FGF21 Promotes Proliferation and Estradiol Synthesis in Porcine Granulosa Cells

“…1E). In addition, timerestricted feeding improves the reproductive functions of female mice through liver FGF21 [31].Furthermore, FGF21 has bene cial effects, which implies that it is a vital positive regulatory factor of follicular development.…”