TY - JOUR

T1 - 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

AU - Haufe, S.

AU - Engeli, S.

AU - Kaminski, J.

AU - Witt, H.

AU - Rein, D.

AU - Kamlage, B.

AU - Utz, W.

AU - Fuhrmann, J. C.

AU - Haas, V.

AU - Mähler, A.

AU - Schulz-Menger, J.

AU - Luft, F. C.

AU - Boschmann, M.

AU - Jordan, J.

N1 - Funding Information: We thank Gritt Stoffels, Anke Strauss, and Elke Nickel-Sczcech for expert technical help with patient recruitment and study procedures. This study was part of a joint project between Metanomics GmbH (Berlin, Germany) and Charité – University Medical School, which was supported by the Federal Ministry of Education and Research ( BMBF–0313868 ), and the German Obesity Network of Competence ( 01 Gl0830 ).

PY - 2017/10

Y1 - 2017/10

N2 - 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.

AB - 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.

KW - Insulin sensitivity

KW - Intramyocellular fat

KW - Weight loss

UR - http://www.scopus.com/inward/record.url?scp=85029813489&partnerID=8YFLogxK

U2 - 10.1016/j.numecd.2017.07.001

DO - 10.1016/j.numecd.2017.07.001

M3 - Article

C2 - 28958691

AN - SCOPUS:85029813489

VL - 27

SP - 858

EP - 864

JO - Nutrition, Metabolism and Cardiovascular Diseases

JF - Nutrition, Metabolism and Cardiovascular Diseases

SN - 0939-4753

IS - 10

ER -