Branched-chain amino acid catabolism rather than amino acids plasma concentrations is associated with diet-induced changes in insulin resistance in overweight to obese individuals

authored by: S. Haufe, S. Engeli, J. Kaminski, H. Witt, D. Rein, B. Kamlage, W. Utz, J. C. Fuhrmann, V. Haas, A. Mähler, J. Schulz-Menger, F. C. Luft, M. Boschmann, J. Jordan
Abstract: Background & aims 3-Hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, which stimulates muscle fatty acid uptake, has been implicated in the pathogenesis of insulin resistance. We tested the hypothesis that circulating 3-HIB herald insulin resistance and that metabolic improvement with weight loss are related to changes in BCAAs and 3-HIB. Methods and results We analyzed plasma and urine in 109 overweight to obese individuals before and after six months on hypocaloric diets reduced in either carbohydrates or fat. We calculated the homeostasis model assessment index (HOMA-IR) and whole body insulin sensitivity from oral glucose tolerance tests and measured intramyocellular fat by magnetic resonance spectroscopy. BCAAs and 3-HIB plasma concentrations were inversely related to insulin sensitivity but not to intramyocellular fat content at baseline. With 7.4 ± 4.5% weight loss mean BCAA and 3-HIB plasma concentrations did not change, irrespective of dietary macronutrient content. Individual changes in 3-HIB with 6-month diet but not BCAAs were correlated to the change in whole body insulin sensitivity and HOMA-IR independently of BMI changes. Conclusions 3-HIB relates to insulin sensitivity but is not associated with intramyocellular fat content in overweight to obese individuals. Moreover, changes in 3-HIB rather than changes in BCAAs are associated with metabolic improvements with weight loss. Registration number for clinical trials: ClinicalTrials.gov Identifier: NCT00956566.
External Organisation(s): Hannover Medical School (MHH)
Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association
Metanomics Health GmbH
HELIOS Klinikum Berlin-Buch
University of Cologne
Charité - Universitätsmedizin Berlin
Type: Article
Journal: Nutrition, Metabolism and Cardiovascular Diseases
Volume: 27
Pages: 858-864
No. of pages: 7
ISSN: 0939-4753
Publication date: 10.2017
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Medicine (miscellaneous), Endocrinology, Diabetes and Metabolism, Nutrition and Dietetics, Cardiology and Cardiovascular Medicine
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1016/j.numecd.2017.07.001 (Access: Closed)