Plasma Concentration of Branched Chain Amino Acids are Not Related to Improvements in Insulin Sensitivity after 12 W of Intensive Exercise in Sedentary Dysglycemic and Normoglycemic Men

2020 ◽  
Author(s):  
Sindre Lee ◽  
Hanne L. Gulseth ◽  
Torgrim M. Langleite ◽  
Frode Norheim ◽  
Thomas Olsen ◽  
...  
2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 529-529
Author(s):  
Chaitra Surugihalli ◽  
Vaishna Muralidaran ◽  
Kruti Patel ◽  
Tabitha Gregory ◽  
Nishanth Sunny

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


2020 ◽  
Vol 98 (11) ◽  
Author(s):  
Woong B Kwon ◽  
Jose A Soto ◽  
Hans H Stein

Abstract Diets based on high levels of corn protein have elevated concentrations of Leu, which may negatively affect N retention in pigs. An experiment was, therefore, conducted to test the hypothesis that Ile and Val supplementation may overcome the detrimental effects of excess dietary Leu on N balance and metabolism of branched-chain amino acids (BCAA) in growing pigs. A total of 144 barrows (initial body weight: 28.5 kg) were housed in metabolism crates and randomly assigned to 1 of 18 dietary treatments. The basal diet contained 0.98% standardized ileal digestible (SID) Lys and had SID Leu, Val, and Ile ratios to SID Lys of 100%, 60%, and 43%, respectively. Crystalline l-Leu (0% or 2.0%), l-Ile (0%, 0.1%, or 0.2%), and l-Val (0%, 0.1%, or 0.2%) were added to the basal diet resulting in a total of 18 dietary treatments that were arranged in a 2 × 3 × 3 factorial. Urine and fecal samples were collected for 5 d after 7 d of adaptation. Blood, skeletal muscle, and liver samples were collected at the conclusion of the experiment. There were no three-way interactions among the main effects. Excess Leu in diets reduced (P < 0.05) N retention and biological value of protein and increased (P < 0.001) plasma urea N (PUN), but PUN was reduced (P < 0.05) as dietary Val increased. Concentrations of Leu in the liver were greater (P < 0.001) in pigs fed excess Leu diets than in pigs fed adequate Leu diets, but concentrations of BCAA in muscle were greater (P < 0.05) in pigs fed low-Leu diets. Increasing dietary Ile increased (P < 0.001) plasma-free Ile and plasma concentration of the Ile metabolite, α-keto-β-methylvalerate, but the increase was greater in diets without excess Leu than in diets with excess Leu (interaction, P < 0.001). Plasma concentrations of Val and the Val metabolite α-keto isovalerate increased (P < 0.001) with increasing dietary Val in diets with adequate Leu, but not in diets with excess Leu (interaction, P < 0.001). Increasing dietary Leu increased (P < 0.001) plasma-free Leu and plasma concentration of the Leu metabolite, α-keto isocaproate (KIC). In contrast, increased dietary Val reduced (P < 0.05) the plasma concentration of KIC. In conclusion, excess dietary Leu reduced N retention and increased PUN in growing pigs, but Val supplementation to excess Leu diets may increase the efficiency of amino acid utilization for protein synthesis as indicated by reduced PUN.


Author(s):  
William O Jonsson ◽  
Jonathan Ponette ◽  
Oscar Horwath ◽  
Tomas Rydenstam ◽  
Karin Söderlund ◽  
...  

Administration of branched-chain amino acids (BCAA) has been suggested to enhance mitochondrial biogenesis, including levels of PGC-1α, which may, in turn, alter kynurenine metabolism. Ten healthy subjects performed 60 min of dynamic one-leg exercise at ~70% of Wmax on two occasions. They were in random order supplied either a mixture of BCAA or flavored water (placebo) during the experiment. Blood samples were collected during exercise and recovery, and muscle biopsies were taken from both legs before, after and 90 and 180 min following exercise. Ingestion of BCAA doubled their concentration in both plasma and muscle while causing a 30-40% reduction (P<0.05 vs. placebo) in levels of aromatic amino acids in both resting and exercising muscle during 3-h recovery. The muscle concentration of kynurenine decreased by 25% (P<0.05) during recovery, similar in both resting and exercising leg and with both supplements, although plasma concentration of kynurenine during recovery was 10% lower (P<0.05) when BCAA were ingested. Ingestion of BCAA reduced the plasma concentration of kynurenic acid by 60% (P<0.01) during exercise and recovery, while the level remained unchanged with placebo. Exercise induced a 3-4-fold increase (P<0.05) in muscle content of PGC-1a1 mRNA after 90 min of recovery under both conditions, whereas levels of KAT4 mRNA and protein were unaffected by exercise or supplement. In conclusion, the reduction of plasma levels of kynurenine and kynurenic acid caused by BCAA were not associated with any changes in the level of muscle kynurenine, suggesting that kynurenine metabolism was altered in tissues other than muscle.


Metabolism ◽  
2000 ◽  
Vol 49 (1) ◽  
pp. 97-100 ◽  
Author(s):  
Tetsuya Yamamoto ◽  
Yuji Moriwaki ◽  
Sumio Takahashi ◽  
Zenta Tsutsumi ◽  
Jun-ichi Yamakita ◽  
...  

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1510 ◽  
Author(s):  
Utpal Prodhan ◽  
Amber Milan ◽  
Eric Thorstensen ◽  
Matthew Barnett ◽  
Ralph Stewart ◽  
...  

Dairy, as a major component of a high protein diet, is a critical dietary source of branched chain amino acids (BCAA), which are biomarkers of health and diseases. While BCAA are known to be key stimulators of protein synthesis, elevated circulatory BCAA is an independent risk factor for type 2 diabetes mellitus. This study examined the impact of altered dairy intake on plasma BCAA and their potential relationship to insulin sensitivity. Healthy adults (n = 102) were randomized to receive dietary advice to reduce, maintain, or increase habitual dairy intake for 1 month. Food intake was recorded with food frequency questionnaires. Self-reported protein intake from dairy was reported to be reduced (−14.6 ± 3.0 g/day), maintained (−4.0 ± 2.0 g/day) or increased (+13.8 ± 4.1 g/day) according to group allocation. No significant alterations in circulating free amino acids (AA), including BCAA, were measured. Insulin sensitivity, as assessed by homeostatic model assessment-insulin resistance (HOMA-IR), was also unaltered. A significant change in dairy protein intake showed no significant effect on fasting circulatory BCAA and insulin sensitivity in healthy populations.


Metabolism ◽  
2014 ◽  
Vol 63 (6) ◽  
pp. 841-850 ◽  
Author(s):  
Fei Xiao ◽  
Junjie Yu ◽  
Yajie Guo ◽  
Jiali Deng ◽  
Kai Li ◽  
...  

2016 ◽  
Vol 5 ◽  
Author(s):  
Annemarie Rietman ◽  
Takara L. Stanley ◽  
Clary Clish ◽  
Vamsi Mootha ◽  
Marco Mensink ◽  
...  

AbstractPlasma branched-chain amino acids (BCAA) are elevated in obesity and associated with increased cardiometabolic risk. β-Aminoisobutyric acid (B-AIBA), a recently identified small molecule metabolite, is associated with decreased cardiometabolic risk. Therefore, we investigated the association of BCAA and B-AIBA with each other and with detailed body composition parameters, including abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A cross-sectional study was carried out with lean (n 15) and obese (n 33) men and women. Detailed metabolic evaluations, including measures of body composition, insulin sensitivity and plasma metabolomics were completed. Plasma BCAA were higher (1·6 (se 0·08) (×107) v. 1·3 (se 0·06) (×107) arbitrary units; P = 0·005) in obese v. lean subjects. BCAA were positively associated with VAT (R 0·49; P = 0·0006) and trended to an association with SAT (R 0·29; P = 0·052). The association between BCAA and VAT, but not SAT, remained significant after controlling for age, sex and race on multivariate modelling (P < 0·05). BCAA were also associated with parameters of insulin sensitivity (Matsuda index: R −0·50, P = 0·0004; glucose AUC: R 0·53, P < 0·001). BCAA were not associated with B-AIBA (R −0·04; P = 0·79). B-AIBA was negatively associated with SAT (R −0·37; P = 0·01) but only trended to an association with VAT (R 0·27; P = 0·07). However, neither relationship remained significant after multivariate modelling (P > 0·05). Plasma B-AIBA was associated with parameters of insulin sensitivity (Matsuda index R 0·36, P = 0·01; glucose AUC: R −0·30, P = 0·04). Plasma BCAA levels were positively correlated with VAT and markers of insulin resistance. The results suggest a possible complex role of adipose tissue in BCAA homeostasis and insulin resistance.


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