Meal sugar-protein balance determines postprandial FGF21 response in humans

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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.

TidsskriftAmerican Journal of Physiology - Endocrinology and Metabolism
Udgave nummer5
Sider (fra-til)E491-E499
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study was supported by a grant from the Independent Research Fund Denmark (Grant Number 0134-00375B). The Novo Nordisk Foundation Center for Basic Metabolic Research is funded by an unconditional donation from the Novo Nordisk Foundation (Grant Number NNF18CC0034900).

Publisher Copyright:
Copyright © 2023 The Authors.

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