Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework

Samantha M. Solon-Biet; Victoria C. Cogger; Tamara Pulpitel; Marika Heblinski; Devin Wahl; Aisling C. McMahon; Alessandra Warren; Jessica Durrant-Whyte; Kirsty A. Walters; James R. Krycer; Fleur Ponton; Rahul Gokarn; Jibran A. Wali; Kari Ruohonen; Arthur D. Conigrave; David E. James; David Raubenheimer; Christopher D. Morrison; David G. Le Couteur; Stephen J. Simpson

doi:10.1016/j.cmet.2016.09.001

Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework

Samantha M. Solon-Biet, Victoria C. Cogger, Tamara Pulpitel, Marika Heblinski, Devin Wahl, Aisling C. McMahon, Alessandra Warren, Jessica Durrant-Whyte, Kirsty A. Walters, James R. Krycer, Fleur Ponton, Rahul Gokarn, Jibran A. Wali, Kari Ruohonen, Arthur D. Conigrave, David E. James, David Raubenheimer, Christopher D. Morrison, David G. Le Couteur, Stephen J. Simpson^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

168 Citations (Scopus)

Abstract

Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved and controversial. Here, we use the Geometric Framework, a nutritional modeling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content. We show that FGF21 was elevated under low protein intakes and maximally when low protein was coupled with high carbohydrate intakes. Our results explain how elevation of FGF21 occurs both under starvation and hyperphagia, and show that the metabolic outcomes associated with elevated FGF21 depend on the nutritional context, differing according to whether the animal is in a state of under- or overfeeding.

Original language	English
Pages (from-to)	555-565
Number of pages	11
Journal	Cell Metabolism
Volume	24
Issue number	4
DOIs	https://doi.org/10.1016/j.cmet.2016.09.001
Publication status	Published - 11 Oct 2016

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Solon-Biet, S. M., Cogger, V. C., Pulpitel, T., Heblinski, M., Wahl, D., McMahon, A. C., Warren, A., Durrant-Whyte, J., Walters, K. A., Krycer, J. R., Ponton, F., Gokarn, R., Wali, J. A., Ruohonen, K., Conigrave, A. D., James, D. E., Raubenheimer, D., Morrison, C. D., Le Couteur, D. G., & Simpson, S. J. (2016). Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework. Cell Metabolism, 24(4), 555-565. https://doi.org/10.1016/j.cmet.2016.09.001

@article{691962439ad1435a8fe26293b1a28e30,

title = "Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework",

abstract = "Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved and controversial. Here, we use the Geometric Framework, a nutritional modeling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content. We show that FGF21 was elevated under low protein intakes and maximally when low protein was coupled with high carbohydrate intakes. Our results explain how elevation of FGF21 occurs both under starvation and hyperphagia, and show that the metabolic outcomes associated with elevated FGF21 depend on the nutritional context, differing according to whether the animal is in a state of under- or overfeeding.",

author = "Solon-Biet, {Samantha M.} and Cogger, {Victoria C.} and Tamara Pulpitel and Marika Heblinski and Devin Wahl and McMahon, {Aisling C.} and Alessandra Warren and Jessica Durrant-Whyte and Walters, {Kirsty A.} and Krycer, {James R.} and Fleur Ponton and Rahul Gokarn and Wali, {Jibran A.} and Kari Ruohonen and Conigrave, {Arthur D.} and James, {David E.} and David Raubenheimer and Morrison, {Christopher D.} and {Le Couteur}, {David G.} and Simpson, {Stephen J.}",

year = "2016",

month = oct,

day = "11",

doi = "10.1016/j.cmet.2016.09.001",

language = "English",

volume = "24",

pages = "555--565",

journal = "Cell Metabolism",

issn = "1550-4131",

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Solon-Biet, SM, Cogger, VC, Pulpitel, T, Heblinski, M, Wahl, D, McMahon, AC, Warren, A, Durrant-Whyte, J, Walters, KA, Krycer, JR, Ponton, F, Gokarn, R, Wali, JA, Ruohonen, K, Conigrave, AD, James, DE, Raubenheimer, D, Morrison, CD, Le Couteur, DG & Simpson, SJ 2016, 'Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework', Cell Metabolism, vol. 24, no. 4, pp. 555-565. https://doi.org/10.1016/j.cmet.2016.09.001

TY - JOUR

T1 - Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework

AU - Solon-Biet, Samantha M.

AU - Cogger, Victoria C.

AU - Pulpitel, Tamara

AU - Heblinski, Marika

AU - Wahl, Devin

AU - McMahon, Aisling C.

AU - Warren, Alessandra

AU - Durrant-Whyte, Jessica

AU - Walters, Kirsty A.

AU - Krycer, James R.

AU - Ponton, Fleur

AU - Gokarn, Rahul

AU - Wali, Jibran A.

AU - Ruohonen, Kari

AU - Conigrave, Arthur D.

AU - James, David E.

AU - Raubenheimer, David

AU - Morrison, Christopher D.

AU - Le Couteur, David G.

AU - Simpson, Stephen J.

PY - 2016/10/11

Y1 - 2016/10/11

N2 - Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved and controversial. Here, we use the Geometric Framework, a nutritional modeling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content. We show that FGF21 was elevated under low protein intakes and maximally when low protein was coupled with high carbohydrate intakes. Our results explain how elevation of FGF21 occurs both under starvation and hyperphagia, and show that the metabolic outcomes associated with elevated FGF21 depend on the nutritional context, differing according to whether the animal is in a state of under- or overfeeding.

AB - Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved and controversial. Here, we use the Geometric Framework, a nutritional modeling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content. We show that FGF21 was elevated under low protein intakes and maximally when low protein was coupled with high carbohydrate intakes. Our results explain how elevation of FGF21 occurs both under starvation and hyperphagia, and show that the metabolic outcomes associated with elevated FGF21 depend on the nutritional context, differing according to whether the animal is in a state of under- or overfeeding.

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UR - http://purl.org/au-research/grants/nhmrc/571328

UR - http://purl.org/au-research/grants/nhmrc/571408

UR - http://purl.org/au-research/grants/arc/DP160101119

UR - http://purl.org/au-research/grants/nhmrc/1110098

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DO - 10.1016/j.cmet.2016.09.001

M3 - Article

C2 - 27693377

AN - SCOPUS:84992315652

SN - 1550-4131

VL - 24

SP - 555

EP - 565

JO - Cell Metabolism

JF - Cell Metabolism

IS - 4

ER -

Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework

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