Differential effects of protein intake versus intake of a defined oligopeptide on FGF-21 in obese human subjects in vivo.
Caseins
/ chemistry
Cross-Over Studies
Diabetes Mellitus, Type 2
/ blood
Dietary Proteins
/ blood
Double-Blind Method
Eating
/ physiology
Female
Fibroblast Growth Factors
/ blood
Hep G2 Cells
Humans
In Vitro Techniques
Insulin Resistance
Male
Middle Aged
Obesity
/ blood
Oligopeptides
/ administration & dosage
Diabetes
FGF-21
Insulin sensitivity
Obesity
Tryptic β-casein hydrolysate
Journal
Clinical nutrition (Edinburgh, Scotland)
ISSN: 1532-1983
Titre abrégé: Clin Nutr
Pays: England
ID NLM: 8309603
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
14
04
2020
revised:
13
05
2020
accepted:
07
06
2020
pubmed:
1
7
2020
medline:
24
8
2021
entrez:
1
7
2020
Statut:
ppublish
Résumé
FGF-21 is described as a powerful metabolic regulator with beneficial effects including glucose-lowering and improvement of insulin sensitivity without hypoglycaemia. On the other hand, FGF-21 is activated when muscle and other tissues are stressed by external effects or internal cellular pathogens that lead to shortcomings in metabolic balance. Previous results suggested that FGF-21 could be a promising target to develop future metabolic therapeutics. The present study was performed to gain deeper insight into the regulation of FGF-21 by protein metabolism in obese human subjects. FGF-21 serum concentrations were measured in a cohort of n = 246 obese humans ± type 2 diabetes mellitus (T2DM) (median age 53.0 [46.0; 60.0] years and BMI 40.43 [35.11; 47.24] kg/m In the cohort analysis, FGF-21 serum concentrations were significant lower with higher protein intake in obese subjects without T2DM but not in obese subjects with T2DM. Furthermore, relative methionine intake was inversely related to FGF-21. While global protein intake in obesity was inversely associated with FGF-21, incubation of HepG2 cells with a β-casein oligopeptide increased FGF-21 expression in vitro. This stimulatory effect was also present in vivo, since in the clinical intervention study treatment of obese subjects with the β-casein oligopeptide for 8 weeks significantly increased FGF-21 serum levels from W0 = 23.86 pg/mL to W8 = 30.54 pg/mL (p < 0.001), while no increase was found for placebo. While the total nutritional protein intake is inversely associated with FGF-21 serum levels, a purified and well characterised oligopeptide is able to induce FGF-21 serum levels in humans. These findings suggest a differential role of various components of protein metabolism on FGF-21, rather than this factor being solely a sensor of total nutritional protein intake.
Sections du résumé
BACKGROUND
FGF-21 is described as a powerful metabolic regulator with beneficial effects including glucose-lowering and improvement of insulin sensitivity without hypoglycaemia. On the other hand, FGF-21 is activated when muscle and other tissues are stressed by external effects or internal cellular pathogens that lead to shortcomings in metabolic balance. Previous results suggested that FGF-21 could be a promising target to develop future metabolic therapeutics.
PURPOSE
The present study was performed to gain deeper insight into the regulation of FGF-21 by protein metabolism in obese human subjects.
METHODS
FGF-21 serum concentrations were measured in a cohort of n = 246 obese humans ± type 2 diabetes mellitus (T2DM) (median age 53.0 [46.0; 60.0] years and BMI 40.43 [35.11; 47.24] kg/m
MAIN FINDINGS
In the cohort analysis, FGF-21 serum concentrations were significant lower with higher protein intake in obese subjects without T2DM but not in obese subjects with T2DM. Furthermore, relative methionine intake was inversely related to FGF-21. While global protein intake in obesity was inversely associated with FGF-21, incubation of HepG2 cells with a β-casein oligopeptide increased FGF-21 expression in vitro. This stimulatory effect was also present in vivo, since in the clinical intervention study treatment of obese subjects with the β-casein oligopeptide for 8 weeks significantly increased FGF-21 serum levels from W0 = 23.86 pg/mL to W8 = 30.54 pg/mL (p < 0.001), while no increase was found for placebo.
CONCLUSION
While the total nutritional protein intake is inversely associated with FGF-21 serum levels, a purified and well characterised oligopeptide is able to induce FGF-21 serum levels in humans. These findings suggest a differential role of various components of protein metabolism on FGF-21, rather than this factor being solely a sensor of total nutritional protein intake.
Identifiants
pubmed: 32600859
pii: S0261-5614(20)30296-X
doi: 10.1016/j.clnu.2020.06.006
pii:
doi:
Substances chimiques
Caseins
0
Dietary Proteins
0
Oligopeptides
0
fibroblast growth factor 21
0
Fibroblast Growth Factors
62031-54-3
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
600-607Informations de copyright
Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest No potential conflicts of interest relevant to this article were reported.