Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21

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...

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Main Authors: Yaxue Cao, Min Yang, Jie Song, Xuemei Jiang, Shengyu Xu, Lianqiang Che, Zhengfeng Fang, Yan Lin, Chao Jin, Bin Feng, De Wu, Lun Hua, Yong Zhuo
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/13/3049
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author Yaxue Cao
Min Yang
Jie Song
Xuemei Jiang
Shengyu Xu
Lianqiang Che
Zhengfeng Fang
Yan Lin
Chao Jin
Bin Feng
De Wu
Lun Hua
Yong Zhuo
author_facet Yaxue Cao
Min Yang
Jie Song
Xuemei Jiang
Shengyu Xu
Lianqiang Che
Zhengfeng Fang
Yan Lin
Chao Jin
Bin Feng
De Wu
Lun Hua
Yong Zhuo
author_sort Yaxue Cao
collection DOAJ
description 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 <i>Kiss</i>-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 <i>Fgf21</i> 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 <i>Kiss</i>-1 were partially required for this process.
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spelling doaj.art-edb675fae9284199bc83d7d6c2e926d42023-11-18T17:16:21ZengMDPI AGNutrients2072-66432023-07-011513304910.3390/nu15133049Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21Yaxue Cao0Min Yang1Jie Song2Xuemei Jiang3Shengyu Xu4Lianqiang Che5Zhengfeng Fang6Yan Lin7Chao Jin8Bin Feng9De Wu10Lun Hua11Yong Zhuo12Key Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaKey Laboratory for Animal Disease Resistant Nutrition of the Ministry of Education, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, ChinaFibroblast 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 <i>Kiss</i>-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 <i>Fgf21</i> 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 <i>Kiss</i>-1 were partially required for this process.https://www.mdpi.com/2072-6643/15/13/3049protein restrictionestrous cycleFGF 21<i>Kiss</i>-1
spellingShingle Yaxue Cao
Min Yang
Jie Song
Xuemei Jiang
Shengyu Xu
Lianqiang Che
Zhengfeng Fang
Yan Lin
Chao Jin
Bin Feng
De Wu
Lun Hua
Yong Zhuo
Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21
Nutrients
protein restriction
estrous cycle
FGF 21
<i>Kiss</i>-1
title Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21
title_full Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21
title_fullStr Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21
title_full_unstemmed Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21
title_short Dietary Protein Regulates Female Estrous Cyclicity Partially via Fibroblast Growth Factor 21
title_sort dietary protein regulates female estrous cyclicity partially via fibroblast growth factor 21
topic protein restriction
estrous cycle
FGF 21
<i>Kiss</i>-1
url https://www.mdpi.com/2072-6643/15/13/3049
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