Effect of the BCAT2 polymorphism (rs11548193) on plasma branched-chain amino acid concentrations after dietary intervention in subjects with obesity and insulin resistance

2021 ◽  
pp. 1-30
Author(s):  
L.E. González-Salazar ◽  
O. Granados-Portillo ◽  
I. Medina-Vera ◽  
E. Pichardo-Ontiveros ◽  
A. Vigil-Martínez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Amino Acid ◽  
Biochemical Parameters ◽  
Dietary Intervention ◽  
Energy Restriction ◽  
Fat Free Mass ◽  
Oral Glucose ◽  
Branched Chain ◽  
Age And Sex

Abstract Background & aims: Branched-chain amino acids (BCAAs) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of a single nucleotide polymorphism (SNP) of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAAs in subjects with obesity and IR. Methods: A prospective cohort study of adult subjects with obesity, body mass index (BMI) ≥ 30 kg/m2, IR (HOMA-IR ≥ 2.5) no diagnosed chronic disease, underwent a DI with an energy restriction of 750 kcal/d and nutritional education for one month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure (REE), oral glucose tolerance test (OGTT) results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNPs were assessed by the TaqMan SNP genotyping assay. Results: A total of 82 subjects were included, 15 subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine, and the sum of BCAAs. Those subjects also had a greater reduction in skeletal muscle mass, fat free mass, total body water, blood pressure, muscle strength and biochemical parameters after one month of the DI and adjusting for age and sex. Conclusions: This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a one-month energy-restricted DI.

scholarly journals Metabolomics analysis reveals altered metabolites in lean compared with obese adolescents and additional metabolic shifts associated with hyperinsulinaemia and insulin resistance in obese adolescents: a cross-sectional study

Metabolomics ◽  
2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Elisabeth Müllner ◽  
Hanna E. Röhnisch ◽  
Claudia von Brömssen ◽  
Ali A. Moazzami
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
Oral Glucose ◽  
Response Level ◽  
Metabolic Alterations ◽  
Obese Adolescents ◽  
Branched Chain ◽  
Metabolomics Analysis

Abstract Introduction Hyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes. Little is known about metabolic alterations separately associated with obesity, hyperinsulinaemia/IR and impaired glucose tolerance (IGT) in adolescents. Objectives To identify metabolic alterations associated with obesity, hyperinsulinaemia/IR and hyperinsulinaemia/IR combined with IGT in obese adolescents. Methods 81 adolescents were stratified into four groups based on body mass index (lean vs. obese), insulin responses (normal insulin (NI) vs. high insulin (HI)) and glucose responses (normal glucose tolerance (NGT) vs. IGT) after an oral glucose tolerance test (OGTT). The groups comprised: (1) healthy lean with NI and NGT, (2) obese with NI and NGT, (3) obese with HI and NGT, and (4) obese with HI and IGT. Targeted nuclear magnetic resonance-based metabolomics analysis was performed on fasting and seven post-OGTT plasma samples, followed by univariate and multivariate statistical analyses. Results Two groups of metabolites were identified: (1) Metabolites associated with insulin response level: adolescents with HI (groups 3–4) had higher concentrations of branched-chain amino acids and tyrosine, and lower concentrations of serine, glycine, myo-inositol and dimethylsulfone, than adolescents with NI (groups 1–2). (2) Metabolites associated with obesity status: obese adolescents (groups 2–4) had higher concentrations of acetylcarnitine, alanine, pyruvate and glutamate, and lower concentrations of acetate, than lean adolescents (group 1). Conclusions Obesity is associated with shifts in fat and energy metabolism. Hyperinsulinaemia/IR in obese adolescents is also associated with increased branched-chain and aromatic amino acids.

scholarly journals Altered metabolomic profiling of overweight and obese adolescents after combined training is associated with reduced insulin resistance

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Renata G. Duft ◽  
Alex Castro ◽  
Ivan L. P. Bonfante ◽  
Wendell A. Lopes ◽  
Larissa R. da Silva ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Exercise Training ◽  
Dietary Intervention ◽  
Metabolic Changes ◽  
Fat Free Mass ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Obese Adolescents ◽  
Combined Training ◽  
Positive Effects

Abstract Exercise training and a healthy diet are the main non-pharmacological strategies for treating chronic conditions, such as obesity and insulin resistance (IR), in adolescents. However, the isolated metabolic changes caused by exercise training without dietary intervention have not yet been established. We investigated how combined training (CT) without dietary intervention altered the concentrations of serum metabolites, biochemical, anthropometric and functional parameters in overweight and obese adolescents. Thirty-seven adolescents (14.6 ± 1.05 years), of both sexes, were randomly assigned to the control group (CG, n = 19) or the training group (TG, n = 18). The CT was composed by resistance training and aerobic training performed in the same session (~ 60 min), three times a week, for 12 weeks. All assessments were performed pre and post-intervention. Metabolomics analyses were conducted using nuclear magnetic resonance spectroscopy (1H NMR) in a 600 MHz spectrometer. There was a decrease in body weight (BW), body mass index (BMI), waist circumference (WC), % body fat (%BF), fasting glucose, insulin levels, and insulin resistance (IR), by HOMA-IR, in the TG. An increase in fat-free mass (FFM) was also observed in the CG. The metabolic changes were given mainly by changes in the levels of metabolites 2-oxoisocaproate (↓TG), 3-hydroxyisobutyrate (↑CG and ↓TG), glucose (↓TG), glutamine (↓CG and ↑TG) and pyruvate (↓TG). These findings demonstrate the positive effects of CT program without dietary intervention on metabolomic profile, body composition, biochemical markers, and glucose metabolism in overweight and obese adolescents.

Amino acid metabolism in the Zucker diabetic fatty rat: effects of insulin resistance and of type 2 diabetes

2004 ◽  
Vol 82 (7) ◽  
pp. 506-514 ◽  
Author(s):  
Enoka P Wijekoon ◽  
Craig Skinner ◽  
Margaret E Brosnan ◽  
John T Brosnan
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Plasma Concentrations ◽  
Branched Chain Amino Acids ◽  
Insulin Resistant ◽  
Branched Chain

We investigated amino acid metabolism in the Zucker diabetic fatty (ZDF Gmi fa/fa) rat during the prediabetic insulin-resistant stage and the frank type 2 diabetic stage. Amino acids were measured in plasma, liver, and skeletal muscle, and the ratios of plasma/liver and plasma/skeletal muscle were calculated. At the insulin-resistant stage, the plasma concentrations of the gluconeogenic amino acids aspartate, serine, glutamine, glycine, and histidine were decreased in the ZDF Gmi fa/fa rats, whereas taurine, α-aminoadipic acid, methionine, phenylalanine, tryptophan, and the 3 branched-chain amino acids were significantly increased. At the diabetic stage, a larger number of gluconeogenic amino acids had decreased plasma concentrations. The 3 branched-chain amino acids had elevated plasma concentrations. In the liver and the skeletal muscles, concentrations of many of the gluconeogenic amino acids were lower at both stages, whereas the levels of 1 or all of the branched-chain amino acids were elevated. These changes in amino acid concentrations are similar to changes seen in type 1 diabetes. It is evident that insulin resistance alone is capable of bringing about many of the changes in amino acid metabolism observed in type 2 diabetes.Key words: plasma amino acids, liver amino acids, muscle amino acids, gluconeogenesis.

scholarly journals Tyrosine Is Associated with Insulin Resistance in Longitudinal Metabolomic Profiling of Obese Children

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Christian Hellmuth ◽  
Franca Fabiana Kirchberg ◽  
Nina Lass ◽  
Ulrike Harder ◽  
Wolfgang Peissner ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Clinical Markers ◽  
Obese Children ◽  
Intervention Programme ◽  
Before And After ◽  
Branched Chain ◽  
One Year

In obese children, hyperinsulinaemia induces adverse metabolic consequences related to the risk of cardiovascular and other disorders. Branched-chain amino acids (BCAA) and acylcarnitines (Carn), involved in amino acid (AA) degradation, were linked to obesity-associated insulin resistance, but these associations yet have not been studied longitudinally in obese children. We studied 80 obese children before and after a one-year lifestyle intervention programme inducing substantial weight loss >0.5 BMI standard deviation scores in 40 children and no weight loss in another 40 children. At baseline and after the 1-year intervention, we assessed insulin resistance (HOMA index), fasting glucose, HbA1c, 2 h glucose in an oral glucose tolerance test, AA, and Carn. BMI adjusted metabolite levels were associated with clinical markers at baseline and after intervention, and changes with the intervention period were evaluated. Only tyrosine was significantly associated with HOMA (p<0.05) at baseline and end and with change during the intervention (p<0.05). In contrast, ratios depicting BCAA metabolism were negatively associated with HOMA at baseline (p<0.05), but not in the longitudinal profiling. Stratified analysis revealed that the children with substantial weight loss drove this association. We conclude that tyrosine alterations in association with insulin resistance precede alteration in BCAA metabolism. This trial is registered with ClinicalTrials.gov IdentifierNCT00435734.

scholarly journals A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance

2016 ◽  
Vol 22 (4) ◽  
pp. 421-426 ◽  
Author(s):  
Cholsoon Jang ◽  
Sungwhan F Oh ◽  
Shogo Wada ◽  
Glenn C Rowe ◽  
Laura Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Amino Acid ◽  
Fatty Acid Transport ◽  
Acid Transport ◽  
Acid Metabolite ◽  
Branched Chain Amino Acid ◽  
Branched Chain
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