Different Proportions of Branched-Chain Amino Acids Modulate Lipid Metabolism in a Finishing Pig Model

2021 ◽  
Author(s):  
Lingyu Zhang ◽  
Fengna Li ◽  
Qiuping Guo ◽  
Yehui Duan ◽  
Wenlong Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lipid Metabolism ◽  
Branched Chain Amino Acids ◽  
Pig Model ◽  
Finishing Pig ◽  
Branched Chain

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

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

scholarly journals The branched‐chain amino acids valine and leucine have differential effects on hepatic lipid metabolism

2020 ◽  
Vol 34 (7) ◽  
pp. 9727-9739
Author(s):  
Christopher A. Bishop ◽  
Matthias B. Schulze ◽  
Susanne Klaus ◽  
Karolin Weitkunat
Keyword(s):  
Amino Acids ◽  
Lipid Metabolism ◽  
Branched Chain Amino Acids ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Differential Effects ◽  
Branched Chain

scholarly journals Impact of Branched Chain Amino Acids on Mitochondrial Metabolism and Insulin Signaling in Mouse Hepatocytes (P08-111-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Meghan Maguire ◽  
Chaitra Surugihalli ◽  
Azuri Hughes ◽  
Nishanth Sunny
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Lipid Metabolism ◽  
Mitochondrial Function ◽  
Insulin Signaling ◽  
Branched Chain Amino Acids ◽  
Turnover Rates ◽  
Alcoholic Fatty Liver ◽  
Gene And Protein Expression ◽  
Branched Chain

Abstract Objectives Plasma branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are elevated during insulin resistance and are robust predictors of future onset of type 2 diabetes mellitus (T2DM). Further, recent evidence points to a significant cross talk between BCAAs and lipid metabolism, which is disrupted during lipid metabolic disorders. Indeed, dysfunctional mitochondrial lipid metabolism is a central feature of non-alcoholic fatty liver disease (NAFLD). Considering the metabolic and molecular mechanisms of BCAA action on central metabolic pathways, we hypothesized that excess BCAAs during insulin resistance can interfere with mitochondrial function, by altering lipid oxidation, gluconeogenesis, and insulin signaling in the liver. Methods Mice (C57BL/6) were either fed a control (10% kcal from fat) or high fat (HF; 60% kcal from fat) diet for 16 weeks. Mice were then overnight fasted and challenged with either a saline or BCAA infusion (15.59 µmole/hour) for 8-hrs. Glucose and ketone turnover rates were determined from the dilution of [13C6]glucose and [13C4]3-hydroxybutyrate tracers. Plasma and tissues were collected and stored for metabolic profiling and gene and protein expression analysis. Results Infusion of BCAAs in mice resulted in a 2-fold elevation of circulating BCAAs (Control 179 ± 7 µM vs. 375 ± 21 µM, P < 0.01, HF 119 ± 4 µM vs. 265 ± 13 µM, P < 0.01). Elevated levels of BCAAs in circulation were associated with an increase in blood glucose levels in control mice (108 ± 7 µM vs. 127 ± 7 µM, p = 0.09). However, this response was absent in HF-fed mice (152 ± 7 µM vs. 155 ± 10 µM, P = 0.85). Surprisingly, ketone turnover rates (µmoles/min) were significantly reduced with BCAA infusion in the control mice (2.5 ± 0.2 vs. 1.6 ± 0.1, P < 0.01), but remained unchanged with BCAA infusion in HF-fed mice (1.9 ± 0.3 vs. 2.0 ± 0.3). The infusion of BCAAs also induced the phosphorylation of Akt in control mice (P < 0.01), but this effect was blunted in HF-fed mice. Conclusions Our results suggest that excess BCAAs can modulate hepatic mitochondrial function and insulin signaling. Chronic exposure to elevated levels of circulating BCAAs could exacerbate metabolic dysfunction during NAFLD by altering normal hepatic mitochondrial function. Funding Sources National Institutes of Health R01.

The Weight Loss Effects of Branched Chain Amino Acids and Vitamin B6: A Randomized Controlled Trial on Obese and Overweight Women

2018 ◽  
Vol 88 (1-2) ◽  
pp. 80-89 ◽  
Author(s):  
Zahra Shakibay Novin ◽  
Saeed Ghavamzadeh ◽  
Alireza Mehdizadeh
Keyword(s):  
Amino Acids ◽  
Weight Loss ◽  
Body Composition ◽  
Vitamin B6 ◽  
Controlled Trial ◽  
Density Lipoprotein ◽  
Branched Chain Amino Acids ◽  
Model Assessment ◽  
Waist To Hip Ratio ◽  
Branched Chain

Abstract. Branched chain amino acids (BCAA), with vitamin B6 have been reported to improve fat metabolism and muscle synthesis. We hypothesized that supplementation with BCAA and vitamin B6 would result in more weight loss and improve body composition and blood markers related to cardiovascular diseases. Our aim was to determine whether the mentioned supplementation would affect weight loss, body composition, and cardiovascular risk factors during weight loss intervention. To this end, we performed a placebo-controlled randomized clinical trial in 42 overweight and obese women (BMI = 25–34.9 kg/m2). Taking a four-week moderate deficit calorie diet (–500 kcal/day), participants were randomized to receive BCAA (6 g/day) with vitamin B6 (40 mg/day) or placebo. Body composition variables measured with the use of bioelectrical impedance analysis, homeostatic model assessment, and plasma insulin, Low density lipoprotein, High density lipoprotein, Total Cholesterol, Triglyceride, and fasting blood sugar were measured. The result indicated that, weight loss was not significantly affected by BCAA and vitamin B6 supplementation (–2.43 ± 1.02 kg) or placebo (–1.64 ± 1.48 kg). However, significant time × treatment interactions in waist to hip ratio (P = 0.005), left leg lean (P = 0.004) and right leg lean (P = 0.023) were observed. Overall, supplementation with BCAA and vitamin B6 could preserve legs lean and also attenuated waist to hip ratio.

Branched chain amino acids decrease top-down event-related potentials in healthy subjects

2007 ◽  
Vol 40 (05) ◽  
Author(s):  
AH Neuhaus ◽  
TE Goldberg ◽  
Y Hassoun ◽  
JA Bates ◽  
KW Nassauer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Healthy Subjects ◽  
Event Related Potentials ◽  
Branched Chain Amino Acids ◽  
Top Down ◽  
Related Potentials ◽  
Branched Chain
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