scholarly journals Branched-Chain Amino Acids Exacerbate Obesity-Related Hepatic Glucose and Lipid Metabolic Disorders via Attenuating Akt2 Signaling

Diabetes ◽  
2020 ◽  
Vol 69 (6) ◽  
pp. 1164-1177 ◽  
Author(s):  
Huishou Zhao ◽  
Fuyang Zhang ◽  
Dan Sun ◽  
Xiong Wang ◽  
Xiaomeng Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Metabolic Disorders ◽  
Branched Chain Amino Acids ◽  
Hepatic Glucose ◽  
Branched Chain

scholarly journals Branched-Chain Amino Acids Exacerbate Obesity-Related Hepatic Glucose and Lipid Metabolic Disorders via Attenuating Akt2 Signaling

2020 ◽  
Author(s):  
Ada Admin ◽  
Huishou Zhao ◽  
Fuyang Zhang ◽  
Dan Sun ◽  
Xiong Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lipid Accumulation ◽  
Metabolic Disorders ◽  
Plasma Lipid ◽  
Branched Chain Amino Acids ◽  
Hepatic Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Hepatic Glucose ◽  
Branched Chain

Branched chain amino acids (BCAAs) are associated with the progression of obesity-related metabolic disorders, including T2DM and non-alcoholic fatty liver disease. However, whether BCAAs disrupt the homeostasis of hepatic glucose and lipid metabolism remains unknown. In this study, we observed that BCAAs supplementation significantly reduced high-fat (HF) diet-induced hepatic lipid accumulation while increasing the plasma lipid levels and promoting muscular and renal lipid accumulation. Further studies demonstrated that BCAAs supplementation significantly increased hepatic gluconeogenesis and suppressed hepatic lipogenesis in HF diet-induced obese (DIO) mice. These phenotypes resulted from severe attenuation of Akt2 signaling via mTORC1- and mTORC2-dependent pathways. BCAAs/branched-chain α-keto acids (BCKAs) chronically suppressed Akt2 activation through mTORC1 and mTORC2 signaling and promoted Akt2 ubiquitin-proteasome-dependent degradation through the mTORC2 pathway. Moreover, the E3 ligase Mul1 played an essential role in BCAAs/BCKAs-mTORC2-induced Akt2 ubiquitin-dependent degradation. We also demonstrated that BCAAs inhibited hepatic lipogenesis by blocking Akt2/SREBP1/INSIG2a signaling and increased hepatic glycogenesis by regulating Akt2/Foxo1 signaling. Collectively, these data demonstrate that in DIO mice, BCAAs supplementation resulted in serious hepatic metabolic disorder and severe liver insulin resistance: insulin failed to not only suppress gluconeogenesis but also activate lipogenesis. Intervening BCAA metabolism is a potential therapeutic target for severe insulin-resistant disease.<br>

scholarly journals Branched-Chain Amino Acids Exacerbate Obesity-Related Hepatic Glucose and Lipid Metabolic Disorders via Attenuating Akt2 Signaling

2020 ◽  
Author(s):  
Ada Admin ◽  
Huishou Zhao ◽  
Fuyang Zhang ◽  
Dan Sun ◽  
Xiong Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lipid Accumulation ◽  
Metabolic Disorders ◽  
Plasma Lipid ◽  
Branched Chain Amino Acids ◽  
Hepatic Lipogenesis ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Hepatic Glucose ◽  
Branched Chain

Branched chain amino acids (BCAAs) are associated with the progression of obesity-related metabolic disorders, including T2DM and non-alcoholic fatty liver disease. However, whether BCAAs disrupt the homeostasis of hepatic glucose and lipid metabolism remains unknown. In this study, we observed that BCAAs supplementation significantly reduced high-fat (HF) diet-induced hepatic lipid accumulation while increasing the plasma lipid levels and promoting muscular and renal lipid accumulation. Further studies demonstrated that BCAAs supplementation significantly increased hepatic gluconeogenesis and suppressed hepatic lipogenesis in HF diet-induced obese (DIO) mice. These phenotypes resulted from severe attenuation of Akt2 signaling via mTORC1- and mTORC2-dependent pathways. BCAAs/branched-chain α-keto acids (BCKAs) chronically suppressed Akt2 activation through mTORC1 and mTORC2 signaling and promoted Akt2 ubiquitin-proteasome-dependent degradation through the mTORC2 pathway. Moreover, the E3 ligase Mul1 played an essential role in BCAAs/BCKAs-mTORC2-induced Akt2 ubiquitin-dependent degradation. We also demonstrated that BCAAs inhibited hepatic lipogenesis by blocking Akt2/SREBP1/INSIG2a signaling and increased hepatic glycogenesis by regulating Akt2/Foxo1 signaling. Collectively, these data demonstrate that in DIO mice, BCAAs supplementation resulted in serious hepatic metabolic disorder and severe liver insulin resistance: insulin failed to not only suppress gluconeogenesis but also activate lipogenesis. Intervening BCAA metabolism is a potential therapeutic target for severe insulin-resistant disease.<br>

Emerging role of branched chain amino acids in metabolic disorders: A mechanistic review

2018 ◽  
Vol 6 (2) ◽  
pp. 47-54 ◽  
Author(s):  
Rohini A. ◽  
Neeraj Agrawal ◽  
Harish Kumar ◽  
Vipin Kumar
Keyword(s):  
Amino Acids ◽  
Metabolic Disorders ◽  
Branched Chain Amino Acids ◽  
Branched Chain

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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