Weight loss and weight maintenance obtained with or without GLP-1 analogue treatment decrease branched chain amino acid levels

Line Engelbrechtsen, Eva Pers Winning Iepsen, Ehm Astrid Andersson Galijatovic, Yuvaraj Mahendran, Julie Rehné Lundgren, Anna Elisabet Jonsson, Sten Madsbad, Jens Juul Holst, Henrik Vestergaard, Torben Hansen, Signe Sørensen Torekov

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Abstract

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.
Original languageEnglish
Article number181
JournalMetabolomics
Volume12
Issue number12
Pages (from-to)1-9
Number of pages9
ISSN1573-3882
DOIs
Publication statusPublished - Dec 2016

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