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

doi:10.1007/s11306-016-1128-0

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

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 language	English
Article number	181
Journal	Metabolomics
Volume	12
Issue number	12
Pages (from-to)	1-9
Number of pages	9
ISSN	1573-3882
DOIs	https://doi.org/10.1007/s11306-016-1128-0
Publication status	Published - 1 Dec 2016

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Engelbrechtsen, L., Iepsen, E. P. W., Galijatovic, E. A. A., Mahendran, Y., Lundgren, J. R., Jonsson, A. E., Madsbad, S., Holst, J. J., Vestergaard, H., Hansen, T., & Torekov, S. S. (2016). Weight loss and weight maintenance obtained with or without GLP-1 analogue treatment decrease branched chain amino acid levels. Metabolomics, 12(12), 1-9. [181]. https://doi.org/10.1007/s11306-016-1128-0

Engelbrechtsen, L, Iepsen, EPW, Galijatovic, EAA, Mahendran, Y, Lundgren, JR, Jonsson, AE, Madsbad, S , Holst, JJ , Vestergaard, H , Hansen, T & Torekov, SS 2016, 'Weight loss and weight maintenance obtained with or without GLP-1 analogue treatment decrease branched chain amino acid levels', Metabolomics, vol. 12, no. 12, 181, pp. 1-9. https://doi.org/10.1007/s11306-016-1128-0

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

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.",

author = "Line Engelbrechtsen and Iepsen, {Eva Pers Winning} and Galijatovic, {Ehm Astrid Andersson} and Yuvaraj Mahendran and Lundgren, {Julie Rehn{\'e}} and Jonsson, {Anna Elisabet} and Sten Madsbad and Holst, {Jens Juul} and Henrik Vestergaard and Torben Hansen and Torekov, {Signe S{\o}rensen}",

year = "2016",

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doi = "10.1007/s11306-016-1128-0",

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journal = "Metabolomics",

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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 - 2016/12/1

Y1 - 2016/12/1

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

SN - 1573-3882

VL - 12

SP - 1

EP - 9

JO - Metabolomics

JF - Metabolomics

IS - 12

M1 - 181

ER -

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

Abstract

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