scholarly journals Differential Effect of Non-Purified and Semi-Purified Standard Diets on Kynurenine and Peripheral Metabolites in Male C57BL/6J Mice

2022 ◽  
Vol 15 ◽  
pp. 117864692110662
Author(s):  
Yuhei Yajima ◽  
Alato Okuno ◽  
Isamu Nakamura ◽  
Teruo Miyazaki ◽  
Akira Honda ◽  
...  
Keyword(s):  
Experimental Data ◽  
Critical Factor ◽  
Branched Chain Amino Acids ◽  
Rodent Models ◽  
Metabolome Analysis ◽  
Peripheral Tissues ◽  
Feed Ingredients ◽  
Branched Chain ◽  
The Brain ◽  
Urine Metabolome

The kynurenine (Kyn) pathway plays crucial roles in several inflammation-induced disorders such as depression. In this study, we measured Kyn and other related molecules in the blood plasma, brain, and urine of male C57BL/6J mice (B6) fed non-purified (MF) and semi-purified (AIN-93G and AIN-93M) standard rodent diets. Mice fed MF had increased plasma Kyn levels compared with those on AIN93-based diets, as well as decreased hippocampal Kyn levels compared with those fed AIN-93G. Previous studies showed that branched chain amino acids (BCAAs) suppress peripheral blood Kyn transportation to the brain, but plasma BCAA levels were not significantly different between the diet groups in our study. Urine metabolome analysis revealed that feed ingredients affected the excretion of many metabolites, and MF-fed mice had elevated excretion of kynurenic and quinolinic acids, pivotal metabolites in the Kyn pathway. Collectively, the level of critical metabolites in the Kyn pathway in the central and peripheral tissues was strongly affected by feed ingredients. Therefore, feed selection is a critical factor to ensure the reproducibility of experimental data in studies involving rodent models.

scholarly journals Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

2020 ◽  
Vol 21 (20) ◽  
pp. 7490
Author(s):  
Jing Xu ◽  
Youseff Jakher ◽  
Rebecca C. Ahrens-Nicklas
Keyword(s):  
Amino Acids ◽  
Maple Syrup Urine Disease ◽  
Attention Deficit Disorder ◽  
Neurological Disorders ◽  
Survival Rates ◽  
Branched Chain Amino Acids ◽  
Maple Syrup ◽  
Urine Disease ◽  
Branched Chain ◽  
The Brain

Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), which catalyzes the irreversible catabolism of branched-chain amino acids (BCAAs). Current management of this BCAA dyshomeostasis consists of dietary restriction of BCAAs and liver transplantation, which aims to partially restore functional BCKDC activity in the periphery. These treatments improve the circulating levels of BCAAs and significantly increase survival rates in MSUD patients. However, significant cognitive and psychiatric morbidities remain. Specifically, patients are at a higher lifetime risk for cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorder. Recent literature suggests that the neurological sequelae may be due to the brain-specific roles of BCAAs. This review will focus on the derangements of BCAAs observed in the brain of MSUD patients and will explore the potential mechanisms driving neurologic dysfunction. Finally, we will discuss recent evidence that implicates the relevance of BCAA metabolism in other neurological disorders. An understanding of the role of BCAAs in the central nervous system may facilitate future identification of novel therapeutic approaches in MSUD and a broad range of neurological disorders.

Amino Acids and Indoleamines in the Brain after Infusion of Branched-Chain Amino Acids to Rats with Liver Ischemia

1986 ◽  
Vol 10 (5) ◽  
pp. 474-478 ◽  
Author(s):  
M. Bugge ◽  
F. Bengtsson ◽  
A. Nobin ◽  
T. Holmin ◽  
B. Jeppsson ◽  
...  
Keyword(s):  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
Liver Ischemia ◽  
Branched Chain ◽  
The Brain

Serotonin Receptors in the Brain following Total Hepatectomy in Rats Treated with Branched-Chain Amino Acids

1989 ◽  
Vol 13 (3) ◽  
pp. 235-239 ◽  
Author(s):  
M. Bugge ◽  
F. Bengtsson ◽  
H. Hall ◽  
I. Wedel ◽  
A. Nobin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Serotonin Receptors ◽  
Branched Chain Amino Acids ◽  
Branched Chain ◽  
The Brain

scholarly journals Factors regulating amino acid release from extrasplanchnic tissues in the rat. Interactions of alanine and glutamine

1975 ◽  
Vol 150 (3) ◽  
pp. 379-387 ◽  
Author(s):  
P J Blackshear ◽  
P A Holloway ◽  
K G Alberti
Keyword(s):  
Amino Acids ◽  
Glutamine Synthetase ◽  
Pyruvate Dehydrogenase ◽  
Alanine Aminotransferase ◽  
Branched Chain Amino Acids ◽  
Peripheral Tissues ◽  
Acid Release ◽  
Branched Chain ◽  
Methionine Sulphoximine

1. Factors regulating the release of alanine and glutamine in vivo were investigated in starved rats by removing the liver from the circulation and monitoring blood metabolite changes for 30 min. 2. Alanine and glutamine were the predominant amino acids released into the circulation in this preparation. 3. Dichloroacetate, an activator of pyruvate dehydrogenase, inhibited net alanine release: it also interfered with the metabolism of the branched-chain amino acids valine, leucine and isoleucine. 4. L-Cycloserine, an inhibitor of alanine aminotransferase, decreased alanine accumulation by 80% after functional hepatectomy, whereas methionine sulphoximine, an inhibitor of glutamine synthetase, decreased glutamine accumulation by the same amount. 5. It was concluded that: (a) the alanine aminotransferase and the glutamine synthetase pathways respectively were responsible for 80% of the alanine and glutamine released into the circulation by the extrasplanchnic tissues, and extrahepatic proteolysis could account for a maximum of 20%; (b) alanine formation by the peripheral tissues was dependent on availability of pyruvate and not of glutamate; (c) glutamate availability could influence glutamine formation subject, possibly, to renal control.

scholarly journals Branched-chain amino acids alter neurobehavioral function in rats

2013 ◽  
Vol 304 (4) ◽  
pp. E405-E413 ◽  
Author(s):  
Anna Coppola ◽  
Brett R. Wenner ◽  
Olga Ilkayeva ◽  
Robert D. Stevens ◽  
Mauro Maggioni ◽  
...  
Keyword(s):  
Amino Acids ◽  
Strong Association ◽  
Aromatic Amino Acids ◽  
High Energy ◽  
Branched Chain Amino Acids ◽  
Synaptic Function ◽  
Behavioral Changes ◽  
Neurobehavioral Function ◽  
Branched Chain ◽  
The Brain

Recently, we have described a strong association of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) with obesity and insulin resistance. In the current study, we have investigated the potential impact of BCAA on behavioral functions. We demonstrate that supplementation of either a high-sucrose or a high-fat diet with BCAA induces anxiety-like behavior in rats compared with control groups fed on unsupplemented diets. These behavioral changes are associated with a significant decrease in the concentration of tryptophan (Trp) in brain tissues and a consequent decrease in serotonin but no difference in indices of serotonin synaptic function. The anxiety-like behaviors and decreased levels of Trp in the brain of BCAA-fed rats were reversed by supplementation of Trp in the drinking water but not by administration of fluoxetine, a selective serotonin reuptake inhibitor, suggesting that the behavioral changes are independent of the serotonergic pathway of Trp metabolism. Instead, BCAA supplementation lowers the brain levels of another Trp-derived metabolite, kynurenic acid, and these levels are normalized by Trp supplementation. We conclude that supplementation of high-energy diets with BCAA causes neurobehavioral impairment. Since BCAA are elevated spontaneously in human obesity, our studies suggest a potential mechanism for explaining the strong association of obesity and mood disorders.

scholarly journals Hepatic Encephalopathy: A Review

2021 ◽  
pp. 89-97
Author(s):  
Savan Kabaria ◽  
Ishita Dalal ◽  
Kapil Gupta ◽  
Abhishek Bhurwal ◽  
Minacapelli Carlos D. ◽  
...  
Keyword(s):  
Amino Acids ◽  
Liver Disease ◽  
Hepatic Encephalopathy ◽  
Hospital Costs ◽  
Branched Chain Amino Acids ◽  
Review Article ◽  
Branched Chain ◽  
New Research ◽  
The Brain ◽  
Recurrence Frequency

Hepatic encephalopathy (HE) is a reversible syndrome observed in patients with liver disease. The syndrome is characterised by a spectrum of neuropsychiatric abnormalities resulting from the accumulation of neurotoxic substances in the bloodstream and ultimately in the brain. HE is a huge burden to patients, caregivers, and the healthcare system. Common treatments for HE, including rifaximin and lactulose, have been shown to reduce the risk of recurrence, frequency of hospitalisations, hospital costs, and mortality. New research and therapeutics exist, including faecal transplants and small-molecule therapies such as branched-chain amino acids. This review article provides a general overview of the current understanding of HE.

scholarly journals Supplementation with Branched-Chain Amino Acids Induces Unexpected Deleterious Effects on Astrocyte Survival and Intracellular Metabolism with or without Hyperammonemia: A Preliminary In Vitro Study

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ting Wang ◽  
Kazuyuki Suzuki ◽  
Toshimi Chiba ◽  
Keisuke Kakisaka ◽  
Yasuhiro Takikawa
Keyword(s):  
Amino Acids ◽  
In Vitro Study ◽  
Branched Chain Amino Acids ◽  
Metabolome Analysis ◽  
Negative Effects ◽  
Human Astrocytes ◽  
Intracellular Metabolism ◽  
Branched Chain ◽  
Underlying Mechanisms

Introduction. Ammonia is a key component in the pathogenesis of hepatic encephalopathy. Branched-chain amino acids (BCAA) have been reported to improve the symptoms of HE induced by hyperammonemia; however, we recently reported that ammonia increases intracellular levels of BCAA and exerts toxic effects on astrocytes. Objectives. This follow-up study was designed to confirm the direct effects of BCAA on human astrocytes and clarify their underlying mechanisms using metabolome analysis and evaluation of associated signaling. Methods. We performed cytotoxicity and cell proliferation tests on astrocytes following BCAA treatment with and without ammonium chloride (NH4Cl) and then compared the results with the effects of BCAA on hepatocytes and neurons. Subsequently, we used metabolomic analysis to investigate intracellular metabolite levels in astrocytes with and without BCAA treatment. Results. The astrocytes showed increased leakage of intracellular lactate dehydrogenase and reduced proliferation rate upon BCAA treatment. Interestingly, our analysis showed a BCAA-induced impairment of intracellular glycolysis/glyconeogenesis as well as amino acid and butyric acid metabolism. Furthermore, BCAA treatment was found to cause decreased levels of Glut-1 and phosphorylated GSK-3β and mTOR in astrocytes. Conclusions. Although further investigations of the effect of BCAA on human astrocytes with hyperammonemia are needed, our work demonstrates that BCAA supplementation has direct negative effects on astrocyte survival and intracellular metabolism.

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.

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