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Article

Modulation of GCN2/eIF2α/ATF4 Pathway in the Liver and Induction of FGF21 in Young Goats Fed a Protein- and/or Phosphorus-Reduced Diet

by
Sarah L. Weber
1,
Karin Hustedt
1,
Nadine Schnepel
1,
Christian Visscher
2 and
Alexandra S. Muscher-Banse
1,*
1
Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, 30173 Hannover, Germany
2
Institute for Animal Nutrition, University of Veterinary Medicine Hannover, 30173 Hannover, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(8), 7153; https://doi.org/10.3390/ijms24087153
Submission received: 7 March 2023 / Revised: 8 April 2023 / Accepted: 10 April 2023 / Published: 12 April 2023
(This article belongs to the Section Molecular Biology)
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Abstract

Mammals respond to amino acid (AA) deficiency by initiating an AA response pathway (AAR) that involves the activation of general control nonderepressible 2 (GCN2), phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), and activation of transcription factor 4 (ATF4). In this study, the effects of protein (N) and/or phosphorus (P) restriction on the GCN2/eIF2α/ATF4 pathway in the liver and the induction of fibroblast growth factor 21 (FGF21) in young goats were investigated. An N-reduced diet resulted in a decrease in circulating essential AA (EAA) and an increase in non-essential AA (NEAA), as well as an increase in hepatic mRNA expression of GCN2 and ATF4 and protein expression of GCN2. Dietary N restriction robustly increased both hepatic FGF21 mRNA expression and circulating FGF21 levels. Accordingly, numerous significant correlations demonstrated the effects of the AA profile on the AAR pathway and confirmed an association. Furthermore, activation of the AAR pathway depended on the sufficient availability of P. When dietary P was restricted, the GCN2/eIF2α/ATF4 pathway was not initiated, and no increase in FGF21 was observed. These results illustrate how the AAR pathway responds to N- and/or P-reduced diets in ruminants, thus demonstrating the complexity of dietary component changes.
Keywords: amino acids; reduced-protein diet; reduced-phosphorus diet; ruminants; FGF21; GCN2; ATF4 amino acids; reduced-protein diet; reduced-phosphorus diet; ruminants; FGF21; GCN2; ATF4
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MDPI and ACS Style

Weber, S.L.; Hustedt, K.; Schnepel, N.; Visscher, C.; Muscher-Banse, A.S. Modulation of GCN2/eIF2α/ATF4 Pathway in the Liver and Induction of FGF21 in Young Goats Fed a Protein- and/or Phosphorus-Reduced Diet. Int. J. Mol. Sci. 2023, 24, 7153. https://doi.org/10.3390/ijms24087153

AMA Style

Weber SL, Hustedt K, Schnepel N, Visscher C, Muscher-Banse AS. Modulation of GCN2/eIF2α/ATF4 Pathway in the Liver and Induction of FGF21 in Young Goats Fed a Protein- and/or Phosphorus-Reduced Diet. International Journal of Molecular Sciences. 2023; 24(8):7153. https://doi.org/10.3390/ijms24087153

Chicago/Turabian Style

Weber, Sarah L., Karin Hustedt, Nadine Schnepel, Christian Visscher, and Alexandra S. Muscher-Banse. 2023. "Modulation of GCN2/eIF2α/ATF4 Pathway in the Liver and Induction of FGF21 in Young Goats Fed a Protein- and/or Phosphorus-Reduced Diet" International Journal of Molecular Sciences 24, no. 8: 7153. https://doi.org/10.3390/ijms24087153

APA Style

Weber, S. L., Hustedt, K., Schnepel, N., Visscher, C., & Muscher-Banse, A. S. (2023). Modulation of GCN2/eIF2α/ATF4 Pathway in the Liver and Induction of FGF21 in Young Goats Fed a Protein- and/or Phosphorus-Reduced Diet. International Journal of Molecular Sciences, 24(8), 7153. https://doi.org/10.3390/ijms24087153

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