TY - JOUR

T1 - Meal sugar-protein balance determines postprandial FGF21 response in humans

AU - Ramne, Stina

AU - Duizer, Lisanne

AU - Nielsen, Mette S.

AU - Jørgensen, Niklas Rye

AU - Svenningsen, Jens S.

AU - Grarup, Niels

AU - Sjödin, Anders

AU - Raben, Anne

AU - Gillum, Matthew P.

N1 - Publisher Copyright: Copyright © 2023 The Authors.

PY - 2023

Y1 - 2023

N2 - Biological mechanisms to promote dietary balance remain unclear. Fibroblast growth factor 21 (FGF21) has been suggested to contribute to such potential regulation considering that FGF21 1) is genetically associated with carbohydrate/sugar and protein intake in opposite directions, 2) is secreted after sugar ingestion and protein restriction, and 3) pharmacologically reduces sugar and increases protein intake in rodents. To gain insight of the nature of this potential regulation, we aimed to study macronutrient interactions in the secretory regulation of FGF21 in healthy humans. We conducted a randomized, double-blinded, crossover meal study (NCT05061485), wherein healthy volunteers consumed a sucrose drink, a sucrose þ protein drink, and a sucrose þ fat drink (matched sucrose content), and compared postprandial FGF21 responses between the three macronutrient combinations. Protein suppressed the sucrose-induced FGF21 secretion [incremental area under the curve (iAUC) for sucrose 484 ± 127 vs. sucrose þ protein -35 ± 49 pg/mL X h, P < 0.001]. The same could not be demonstrated for fat (iAUC 319 ± 102 pg/mL X h, P ¼ 203 for sucrose þ fat vs. sucrose). We found no indications that regulators of glycemic homeostasis could explain this effect. This indicates that FGF21 responds to disproportionate intake of sucrose relative to protein acutely within a meal, and that protein outweighs sucrose in FGF21 regulation. Together with previous findings, our results suggests that FGF21 might act to promote macronutrient balance and sufficient protein intake.

AB - Biological mechanisms to promote dietary balance remain unclear. Fibroblast growth factor 21 (FGF21) has been suggested to contribute to such potential regulation considering that FGF21 1) is genetically associated with carbohydrate/sugar and protein intake in opposite directions, 2) is secreted after sugar ingestion and protein restriction, and 3) pharmacologically reduces sugar and increases protein intake in rodents. To gain insight of the nature of this potential regulation, we aimed to study macronutrient interactions in the secretory regulation of FGF21 in healthy humans. We conducted a randomized, double-blinded, crossover meal study (NCT05061485), wherein healthy volunteers consumed a sucrose drink, a sucrose þ protein drink, and a sucrose þ fat drink (matched sucrose content), and compared postprandial FGF21 responses between the three macronutrient combinations. Protein suppressed the sucrose-induced FGF21 secretion [incremental area under the curve (iAUC) for sucrose 484 ± 127 vs. sucrose þ protein -35 ± 49 pg/mL X h, P < 0.001]. The same could not be demonstrated for fat (iAUC 319 ± 102 pg/mL X h, P ¼ 203 for sucrose þ fat vs. sucrose). We found no indications that regulators of glycemic homeostasis could explain this effect. This indicates that FGF21 responds to disproportionate intake of sucrose relative to protein acutely within a meal, and that protein outweighs sucrose in FGF21 regulation. Together with previous findings, our results suggests that FGF21 might act to promote macronutrient balance and sufficient protein intake.

KW - fibroblast growth factor 21

KW - macronutrient balance

KW - meal study

KW - protein

KW - sucrose

U2 - 10.1152/ajpendo.00241.2023

DO - 10.1152/ajpendo.00241.2023

M3 - Journal article

C2 - 37729024

AN - SCOPUS:85174750890

VL - 325

SP - E491-E499

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 5

ER -