Key Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China.
Pet Nutrition and Health Research Center, Chengdu Agricultural College, Chengdu 611130, China.
Nutrients. 2023 Jul 6;15(13):3049. doi: 10.3390/nu15133049.
Fibroblast growth factor 21 (FGF21), a hormone predominantly released in the liver, has emerged as a critical endocrine signal of dietary protein intake, but its role in the control of estrous cyclicity by dietary protein remains uncertain. To investigated the role of FGF21 and hypothalamic changes in the regulation of estrous cyclicity by dietary protein intake, female adult Sprague-Dawley rats with normal estrous cycles were fed diets with protein contents of 4% (P4), 8% (P8), 13% (P13), 18% (P18), and 23% (P23). FGF21 liver-specific knockout or wild-type mice were fed P18 or P4 diets to examine the role of liver FGF21 in the control of estrous cyclicity. Dietary protein restriction resulted in no negative effects on estrous cyclicity or ovarian follicular development when the protein content was greater than 8%. Protein restriction at 4% resulted in decreased bodyweight, compromised -1 expression in the hypothalamus, disturbed estrous cyclicity, and inhibited uterine and ovarian follicular development. The disturbed estrous cyclicity in rats that received the P4 diet was reversed after feeding with the P18 diet. Liver mRNA expressions and serum FGF21 levels were significantly increased as dietary protein content decreased, and loss of hepatic FGF21 delayed the onset of cyclicity disruption in rats fed with the P4 diet, possibly due to the regulation of insulin-like growth factor-1. Collectively, severe dietary protein restriction results in the cessation of estrous cyclicity and ovarian follicle development, and hepatic FGF21 and hypothalamic -1 were partially required for this process.
成纤维细胞生长因子 21（FGF21）是一种主要在肝脏中释放的激素，已成为膳食蛋白质摄入的关键内分泌信号，但它在膳食蛋白质控制动情周期中的作用尚不确定。为了研究 FGF21 和下丘脑在膳食蛋白质摄入调节动情周期中的作用，正常动情周期的成年 Sprague-Dawley 雌性大鼠用蛋白质含量为 4%（P4）、8%（P8）、13%（P13）、18%（P18）和 23%（P23）的饮食喂养。用 P18 或 P4 饮食喂养 FGF21 肝特异性敲除或野生型小鼠，以研究肝脏 FGF21 在控制动情周期中的作用。当蛋白质含量大于 8%时，蛋白质限制对动情周期或卵巢卵泡发育没有负面影响。当蛋白质含量为 4%时，蛋白质限制导致体重减轻，下丘脑-1 表达受损，动情周期紊乱，子宫和卵巢卵泡发育受到抑制。接受 P4 饮食的大鼠的紊乱动情周期在改用 P18 饮食后得到逆转。随着膳食蛋白质含量的降低，肝脏 mRNA 表达和血清 FGF21 水平显著增加，而肝 FGF21 的丧失延迟了 P4 饮食喂养大鼠的周期性紊乱的发生，这可能是由于胰岛素样生长因子-1的调节。总之，严重的膳食蛋白质限制导致动情周期和卵巢卵泡发育停止，而肝脏 FGF21 和下丘脑-1 部分参与了这一过程。
