TY - JOUR
T1 - Weight loss and weight maintenance obtained with or without GLP-1 analogue treatment decrease branched chain amino acid levels
AU - Engelbrechtsen, Line
AU - Iepsen, Eva Pers Winning
AU - Galijatovic, Ehm Astrid Andersson
AU - Mahendran, Yuvaraj
AU - Lundgren, Julie Rehné
AU - Jonsson, Anna Elisabet
AU - Madsbad, Sten
AU - Holst, Jens Juul
AU - Vestergaard, Henrik
AU - Hansen, Torben
AU - Torekov, Signe Sørensen
PY - 2016/12
Y1 - 2016/12
N2 - Introduction
Increased levels of circulating branched chain amino acids (BCAAs), as well as phenylalanine, and tyrosine have been suggested to be involved in the pathogenesis of insulin resistance and type 2 diabetes. However, it is unknown how these metabolites are affected by weight loss, and during weight-maintaining treatment with glucagon-like peptide-1 receptor agonist (GLP-1 RA).
Objective
We aimed to characterize changes in metabolites related to protein turnover and glycolysis after a weight loss intervention followed by long term weight maintenance with/without GLP-1 RA.
Methods
Fifty-eight obese individuals underwent a diet-induced 12 % body weight loss during 8 weeks. Participants were randomized to weight maintenance with or without administration of the GLP-1 RA liraglutide (1.2 mg/day) for 52 weeks. Metabolomic profiling by high-throughput proton nuclear magnetic resonance spectroscopy was used for quantification of metabolites.
Results
The weight loss was maintained in both groups and was associated with 9–20 % decreases in plasma concentrations of alanine, phenylalanine, histidine, tyrosine and the BCAAs leucine, isoleucine and valine (p < 0.05). Plasma citrate levels increased during weight loss (p = 5.2 × 10−15) and showed inverse correlation with insulin resistance measured by HOMA–IR levels (r = −0.318, p = 0.025). Valine concentrations were lower in the control group compared to the GLP-1RA group during weight maintenance (p = 0.005).
Conclusion
Weight loss is associated with marked changes in plasma concentrations of eight amino acids and glycolysis-related metabolites. Levels of the suggested type 2 diabetes risk markers (BCAAs) remain low during long-term weight maintenance.
AB - Introduction
Increased levels of circulating branched chain amino acids (BCAAs), as well as phenylalanine, and tyrosine have been suggested to be involved in the pathogenesis of insulin resistance and type 2 diabetes. However, it is unknown how these metabolites are affected by weight loss, and during weight-maintaining treatment with glucagon-like peptide-1 receptor agonist (GLP-1 RA).
Objective
We aimed to characterize changes in metabolites related to protein turnover and glycolysis after a weight loss intervention followed by long term weight maintenance with/without GLP-1 RA.
Methods
Fifty-eight obese individuals underwent a diet-induced 12 % body weight loss during 8 weeks. Participants were randomized to weight maintenance with or without administration of the GLP-1 RA liraglutide (1.2 mg/day) for 52 weeks. Metabolomic profiling by high-throughput proton nuclear magnetic resonance spectroscopy was used for quantification of metabolites.
Results
The weight loss was maintained in both groups and was associated with 9–20 % decreases in plasma concentrations of alanine, phenylalanine, histidine, tyrosine and the BCAAs leucine, isoleucine and valine (p < 0.05). Plasma citrate levels increased during weight loss (p = 5.2 × 10−15) and showed inverse correlation with insulin resistance measured by HOMA–IR levels (r = −0.318, p = 0.025). Valine concentrations were lower in the control group compared to the GLP-1RA group during weight maintenance (p = 0.005).
Conclusion
Weight loss is associated with marked changes in plasma concentrations of eight amino acids and glycolysis-related metabolites. Levels of the suggested type 2 diabetes risk markers (BCAAs) remain low during long-term weight maintenance.
U2 - 10.1007/s11306-016-1128-0
DO - 10.1007/s11306-016-1128-0
M3 - Journal article
VL - 12
SP - 1
EP - 9
JO - Metabolomics
JF - Metabolomics
SN - 1573-3882
IS - 12
M1 - 181
ER -