Gut microbiota mediate the FGF21 adaptive stress response to chronic dietary protein-restriction in mice

Anthony Martin, Gertrude Ecklu-Mensah, Connie W. Y. Ha, Gustaf Hendrick, Donald K. Layman, Jack Gilbert and Suzanne Devkota ()
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Anthony Martin: Cedars-Sinai Medical Center
Gertrude Ecklu-Mensah: University of California San Diego
Connie W. Y. Ha: Cedars-Sinai Medical Center
Gustaf Hendrick: Cedars-Sinai Medical Center
Donald K. Layman: University of Illinois
Jack Gilbert: University of California San Diego
Suzanne Devkota: Cedars-Sinai Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Chronic dietary protein-restriction can create essential amino acid deficiencies and induce metabolic adaptation through the hepatic FGF21 pathway which serves to maintain host fitness during prolonged states of nutritional imbalance. Similarly, the gut microbiome undergoes metabolic adaptations when dietary nutrients are added or withdrawn. Here we confirm previous reports that dietary protein-restriction triggers the hepatic FGF21 adaptive metabolic pathway and further demonstrate that this response is mediated by the gut microbiome and can be tuned through dietary supplementation of fibers that alter the gut microbiome. In the absence of a gut microbiome, we discover that FGF21 is de-sensitized to the effect of protein-restriction. These data suggest that host-intrinsic adaptive pathways to chronic dietary protein-restriction, such as the hepatic FGF21 pathway, may in-fact be responding first to adaptive metabolic changes in the gut microbiome.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24074-z

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DOI: 10.1038/s41467-021-24074-z

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