Branched-Chain Amino Acids and Insulin Metabolism: The Insulin Resistance Atherosclerosis Study (IRAS)

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.

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Targeted metabolomic analysis reveals the association between the postprandial change in palmitic acid, branched-chain amino acids and insulin resistance in young obese subjects

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2015.01.014 ◽

2015 ◽

Vol 108 (1) ◽

pp. 84-93 ◽

Cited By ~ 22

Author(s):

Liyan Liu ◽

Rennan Feng ◽

Fuchuan Guo ◽

Ying Li ◽

Jundong Jiao ◽

...

Keyword(s):

Insulin Resistance ◽

Amino Acids ◽

Palmitic Acid ◽

Branched Chain Amino Acids ◽

Metabolomic Analysis ◽

Obese Subjects ◽

Branched Chain

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Branched-chain amino acids suppress the cumulative recurrence of hepatocellular carcinoma under conditions of insulin-resistance

Oncology Reports ◽

10.3892/or.2013.2497 ◽

2013 ◽

Vol 30 (2) ◽

pp. 545-552 ◽

Cited By ~ 9

Author(s):

HITOSHI YOSHIJI ◽

RYUICHI NOGUCHI ◽

TADASHI NAMISAKI ◽

KEI MORIYA ◽

MITSUTERU KITADE ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Insulin Resistance ◽

Amino Acids ◽

Branched Chain Amino Acids ◽

Branched Chain

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Chronic Dietary Branched-Chain Amino Acids Induced Lipid Oxidation and Blunted Insulin-Stimulated Glucose Production in Mice With NAFLD

Current Developments in Nutrition ◽

10.1093/cdn/nzab041_044 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 529-529

Author(s):

Chaitra Surugihalli ◽

Vaishna Muralidaran ◽

Kruti Patel ◽

Tabitha Gregory ◽

Nishanth Sunny

Keyword(s):

Insulin Resistance ◽

Amino Acids ◽

Lipid Metabolism ◽

Insulin Sensitivity ◽

Lipid Oxidation ◽

Glucose Production ◽

Branched Chain Amino Acids ◽

Hepatic Insulin Resistance ◽

High Fat ◽

Branched Chain

Abstract Objectives Elevated circulating branched-chain amino acids (BCAAs) during insulin resistance are strong predictors of type 2 diabetes mellitus onset. Defects in BCAA degradation are evident in several tissues during insulin resistance and non-alcoholic fatty liver disease (NAFLD). Furthermore, alterations in BCAA metabolism are associated with changes in several aspects lipid metabolism, including lipogenesis, ketogenesis and mitochondrial TCA cycle activity. Considering the crosstalk between BCAAs and lipid metabolism, we hypothesized that chronic supplementation of BCAAs will modulate hepatic insulin resistance and mitochondrial lipid oxidation during NAFLD. Methods Mice (C57BL/6N) were reared on either a low-fat (LF; 10% fat kcal), high-fat (HF; 60% fat kcal or high-fat diet supplemented with BCAA (HFBA; 150% BCAA) for 24 weeks. Metabolic profiling was conducted under fed or overnight fasted (14–16 hrs) conditions. A subset of overnight fasted mice from the HF and HFBA groups were subjected to hyperinsulinemic euglycemic clamps, following implantation of jugular vein catheters. Results Feeding HF and HFBA diets resulted in NAFLD. Circulating BCAAs were higher in ‘fed’ mice consuming HFBA diet (e.g., Valine, µM ± SEM; 311 ± 38 in HF, 432 ± 34 in HFBA, P ≤ 0.05). Overnight fasting significantly reduced BCAA levels in all groups, but the fasting levels of BCAAs remained similar between groups. Fed-to-fasted fold changes in blood glucose, serum insulin and c-peptide were higher in HFBA mice (P ≤ 0.05). Insulin stimulated suppression of glucose production (% ± SEM; HF = 38 ± 11, HFBA = 16 ± 16) was blunted in HFBA mice. Furthermore, fed-to-fasted expression of hepatic genes involved in lipid oxidation, including LCAD, MCAD, PPARa and CPT1a were significantly higher (P ≤ 0.05) in the HFBA mice. Conclusions In summary, chronic BCAA supplementation induced hepatic lipid oxidation gene expression, without any apparent improvements in insulin sensitivity. In conclusion, while the induction of lipid oxidation by BCAAs could explain certain beneficial effects associated with their supplementation, the longer-term impact of the BCAAs on insulin sensitivity need to be further explored. Funding Sources National Institutes of Health (NIH) grant RO1-DK-112865

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Lipoprotein insulin resistance score and branched-chain amino acids increase after adrenalectomy for unilateral aldosterone-producing adenoma: a preliminary study

Endocrine ◽

10.1007/s12020-020-02235-2 ◽

2020 ◽

Vol 68 (2) ◽

pp. 420-426

Author(s):

Christian Adolf ◽

Annika M. A. Berends ◽

Margery A. Connelly ◽

Martin Reincke ◽

Robin P. F. Dullaart

Keyword(s):

Insulin Resistance ◽

Amino Acids ◽

Branched Chain Amino Acids ◽

Aldosterone Producing Adenoma ◽

Preliminary Study ◽

Branched Chain ◽

Resistance Score

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1934-P: Branched-Chain Amino Acids Are Poor Markers of Insulin Resistance in Women: The Federal Women’s Study

Diabetes ◽

10.2337/db20-1934-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 1934-P

Author(s):

SAMANTHA MATTA ◽

CELESTE K. CRAVALHO ◽

ALFREDO VILLALOBOS-PEREZ ◽

ABBY MEYERS ◽

LILIAN MABUNDO ◽

...

Keyword(s):

Insulin Resistance ◽

Amino Acids ◽

Branched Chain Amino Acids ◽

Branched Chain

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Abstract 048: Circulating Branched-Chain Amino Acids and Incident Cardiovascular Disease in a Prospective Cohort of US Women

Circulation ◽

10.1161/circ.137.suppl_1.048 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Deirdre K Tobias ◽

Patrick R Lawler ◽

Paulo H Harada ◽

Olga V Demler ◽

Paul M Ridker ◽

...

Keyword(s):

Insulin Resistance ◽

Cardiovascular Disease ◽

Amino Acids ◽

Prospective Cohort ◽

Branched Chain Amino Acids ◽

Health Study ◽

Blood Collection ◽

Cvd Risk ◽

Isoleucine Leucine ◽

Branched Chain

Introduction: Recent metabolomics studies have identified circulating levels of branched-chain amino acids (BCAAs; isoleucine, leucine, valine) as strong predictors of type 2 diabetes (T2D). Whether BCAAs are implicated in cardiovascular disease (CVD) risk has not been established. Hypothesis: We hypothesized that higher baseline levels of plasma BCAAs are associated with an elevated risk of incident CVD events, and evaluated whether this relationship was dependent on an intermediate diagnosis of T2D. Methods: Participants enrolled in the Women’s Health Study prospective cohort were eligible if they did not report CVD or cancer prior to baseline blood collection (N=27,172, mean baseline age=54.7 years). Plasma BCAA metabolites were measured via proton NMR spectroscopy, ln-transformed, and standardized for analysis. We used multivariable Cox proportional regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) per standard deviation (SD) of total and individual BCAAs with incident CVD (myocardial infarction [MI], stroke, coronary revascularization). Results: 1,917 confirmed CVD events occurred over follow-up (mean 18.6 years). In models adjusted for age, body mass index, smoking status, diet quality, physical activity, and other established CVD risk factors, total BCAAs were positively associated with CVD (per SD, HR=1.13, CI=1.08 to 1.19), comparable in magnitude to the association of LDL cholesterol with CVD (per SD, HR=1.15, CI=1.09 to 1.21). In particular, BCAAs were associated with coronary events (MI: HR=1.21, CI=1.10 to 1.33; revascularization: HR=1.15, CI=1.07 to 1.23), but not with stroke (HR=1.07, CI=0.98 to 1.15). The BCAA-CVD relationship was notably greater (p-interaction=0.008) among participants who developed T2D prior to a CVD event (HR=1.25, CI=1.13 to 1.39), vs. women without T2D (HR=1.07, CI=1.01 to 1.13). Isoleucine, leucine, and valine were each associated with CVD (p<0.05). Further adjusting for biomarkers of potential intermediates, HbA1c, lipids, and a lipoprotein-based insulin resistance score entirely eliminated the associations of BCAAs with CVD. Conclusions: Circulating plasma BCAAs were positively associated with long-term incident CVD in a cohort of US women, in particular among women who developed T2D prior to a CVD event. Impaired BCAA metabolism may represent a shared pathway of insulin resistance that links the risks of T2D and CVD.

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