PMID- 32600859
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20210823
IS  - 1532-1983 (Electronic)
IS  - 0261-5614 (Linking)
VI  - 40
IP  - 2
DP  - 2021 Feb
TI  - Differential effects of protein intake versus intake of a defined oligopeptide on 
      FGF-21 in obese human subjects in vivo.
PG  - 600-607
LID - S0261-5614(20)30296-X [pii]
LID - 10.1016/j.clnu.2020.06.006 [doi]
AB  - 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(2)) and related to the nutritional protein intake. In 
      addition, the effect of a novel oligopeptide purified from a beta-casein hydrolysate 
      on FGF-21 was examined in vitro in liver cells and in vivo in a human 
      intervention study with the main focus on metabolic inflammation including 40 
      mainly obese subjects (mean age 41.08 +/- 9.76 years, mean BMI 38.29 +/- 9.4 kg/m(2)) 
      in a randomized 20 weeks double-blind cross-over design. 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 beta-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 beta-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.
CI  - Copyright (c) 2020 Elsevier Ltd and European Society for Clinical Nutrition and 
      Metabolism. All rights reserved.
FAU - Fangmann, Daniela
AU  - Fangmann D
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany.
FAU - Geisler, Corinna
AU  - Geisler C
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany.
FAU - Schlicht, Kristina
AU  - Schlicht K
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany.
FAU - Hartmann, Katharina
AU  - Hartmann K
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany.
FAU - Kopke, Jana
AU  - Kopke J
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany.
FAU - Tiede, Anika
AU  - Tiede A
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany.
FAU - Settgast, Ute
AU  - Settgast U
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany.
FAU - Turk, Kathrin
AU  - Turk K
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany.
FAU - Schulte, Dominik M
AU  - Schulte DM
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany.
FAU - Altmann, Karina
AU  - Altmann K
AD  - Max Rubner-Institute, Federal Research Institute of Nutrition and Food, 
      Department of Safety and Quality of Milk and Fish Products, Kiel, 24103, Germany.
FAU - Clawin-Radecker, Ingrid
AU  - Clawin-Radecker I
AD  - Max Rubner-Institute, Federal Research Institute of Nutrition and Food, 
      Department of Safety and Quality of Milk and Fish Products, Kiel, 24103, Germany.
FAU - Lorenzen, Peter Ch
AU  - Lorenzen PC
AD  - Max Rubner-Institute, Federal Research Institute of Nutrition and Food, 
      Department of Safety and Quality of Milk and Fish Products, Kiel, 24103, Germany.
FAU - Schreiber, Stefan
AU  - Schreiber S
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany; Institute of Clinical Molecular 
      Biology, University Hospital Schleswig-Holstein, Campus Kiel, University of Kiel, 
      Kiel, 24118, Germany.
FAU - Schwarz, Karin
AU  - Schwarz K
AD  - University of Kiel, Department of Food Technology, University of Kiel, Kiel, 
      24118, Germany.
FAU - Laudes, Matthias
AU  - Laudes M
AD  - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of 
      Internal Medicine 1, University Hospital Schleswig-Holstein, Campus Kiel, 
      University of Kiel, Kiel, 24105, Germany. Electronic address: 
      matthias.laudes@uksh.de.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200617
PL  - England
TA  - Clin Nutr
JT  - Clinical nutrition (Edinburgh, Scotland)
JID - 8309603
RN  - 0 (Caseins)
RN  - 0 (Dietary Proteins)
RN  - 0 (Oligopeptides)
RN  - 0 (fibroblast growth factor 21)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Caseins/chemistry
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/blood/complications
MH  - Dietary Proteins/*blood
MH  - Double-Blind Method
MH  - Eating/*physiology
MH  - Female
MH  - Fibroblast Growth Factors/*blood
MH  - Hep G2 Cells
MH  - Humans
MH  - In Vitro Techniques
MH  - Insulin Resistance
MH  - Male
MH  - Middle Aged
MH  - Obesity/*blood/complications
MH  - Oligopeptides/*administration & dosage
OTO - NOTNLM
OT  - Diabetes
OT  - FGF-21
OT  - Insulin sensitivity
OT  - Obesity
OT  - Tryptic beta-casein hydrolysate
COIS- Conflicts of interest No potential conflicts of interest relevant to this article 
      were reported.
EDAT- 2020/07/01 06:00
MHDA- 2021/08/24 06:00
CRDT- 2020/07/01 06:00
PHST- 2020/04/14 00:00 [received]
PHST- 2020/05/13 00:00 [revised]
PHST- 2020/06/07 00:00 [accepted]
PHST- 2020/07/01 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PHST- 2020/07/01 06:00 [entrez]
AID - S0261-5614(20)30296-X [pii]
AID - 10.1016/j.clnu.2020.06.006 [doi]
PST - ppublish
SO  - Clin Nutr. 2021 Feb;40(2):600-607. doi: 10.1016/j.clnu.2020.06.006. Epub 2020 Jun 
      17.