scholarly journals NMR-Based Metabonomic Study Reveals Intervention Effects of Polydatin on Potassium Oxonate-Induced Hyperuricemia in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Bin Han ◽  
Mengjuan Gong ◽  
Zhong Li ◽  
Yuqin Qiu ◽  
Zhongjie Zou
Keyword(s):  
Ketone Bodies ◽  
Tricarboxylic Acid Cycle ◽  
Therapeutic Effects ◽  
Holistic View ◽  
Branched Chain Amino Acid ◽  
Metabolic Mechanism ◽  
Branched Chain ◽  
Underlying Mechanisms ◽  
Natural Precursor ◽  
Potassium Oxonate

Previous studies have disclosed the antihyperuricemic effect of polydatin, a natural precursor of resveratrol; however, the mechanisms of action still remain elusive. The present study was undertaken to evaluate the therapeutic effects and the underlying mechanisms of polydatin on potassium oxonate-induced hyperuricemia in rats through metabonomic technology from a holistic view. Nuclear magnetic resonance (NMR) spectroscopy was applied to capture the metabolic changes in sera and urine collected from rats induced by hyperuricemia and polydatin treatment. With multivariate data analysis, significant metabolic perturbations were observed in hyperuricemic rats compared with the healthy controls. A total of eleven and six metabolites were identified as differential metabolites related to hyperuricemia in serum and urine of rats, respectively. The proposed pathways primarily included branched-chain amino acid (BCAA) metabolism, glycolysis, the tricarboxylic acid cycle, synthesis and degradation of ketone bodies, purine metabolism, and intestinal microflora metabolism. Additionally, some metabolites indicated the risk of renal injury induced by hyperuricemia. Polydatin significantly lowered the levels of serum uric acid, creatinine, and blood urea nitrogen and alleviated the abnormal metabolic status in hyperuricemic rats by partially restoring the balance of the perturbed metabolic pathways. Our findings shed light on the understanding of the pathophysiological process of hyperuricemia and provided a reference for revealing the metabolic mechanism produced by polydatin in the treatment of hyperuricemia.

Low glycogen and branched-chain amino acid ingestion do not impair anaplerosis during exercise in humans

1999 ◽  
Vol 87 (5) ◽  
pp. 1662-1667 ◽  
Author(s):  
Martin J. Gibala ◽  
Marco Lozej ◽  
Mark A. Tarnopolsky ◽  
Cyndy McLean ◽  
Terry E. Graham
Keyword(s):  
Amino Acid ◽  
Muscle Glycogen ◽  
Tricarboxylic Acid Cycle ◽  
Total Concentration ◽  
Exercise Bout ◽  
Branched Chain Amino Acid ◽  
Branched Chain ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Rate Limiting ◽  
Exercise In Humans

We examined the hypothesis that increasing the rate of branched-chain amino acid (BCAA) oxidation, during conditions of low glycogen availability, reduces the level of muscle tricarboxylic acid cycle intermediates (TCAI) by placing a carbon “drain” on the cycle at the level of 2-oxoglutarate. Six men cycled at ∼70% of maximal oxygen uptake for 15 min under two conditions: 1) low preexercise muscle glycogen (placebo) and 2) low glycogen combined with BCAA ingestion. We have previously shown that BCAA ingestion increased the activity of branched-chain oxoacid dehydrogenase, the rate-limiting enzyme for BCAA oxidation in muscle, compared with low glycogen alone [M. L. Jackman, M. J. Gibala, E. Hultman, and T. E. Graham. Am. J. Physiol. 272 ( Endocrinol. Metab. 35): E233–E238, 1997]. Muscle glycogen concentration was 185 ± 22 and 206 ± 22 mmol/kg dry wt at rest for the placebo and BCAA-supplemented trials, respectively, and decreased to 109 ± 18 and 96 ± 10 mmol/kg dry wt after exercise. The net increase in the total concentration of six measured TCAI (∼95% of TCAI pool) during exercise was not different between trials (3.97 ± 0.34 vs. 3.88 ± 0.34 mmol/kg dry wt for the placebo and BCAA trials, respectively). Muscle 2-oxoglutarate concentration decreased from ∼0.05 at rest to ∼0.03 mmol/kg dry wt after exercise in both trials. The magnitude of TCAI pool expansion in both trials was similar to that seen previously in subjects who performed an identical exercise bout after a normal mixed diet [M. J. Gibala, M. A. Tarnopolsky, and T. E. Graham. Am. J. Physiol. 272 ( Endocrinol. Metab. 35): E239–E244, 1997]. These data suggest that increasing the rate of BCAA oxidation has no measurable effect on muscle TCAI during exercise with low glycogen in humans. Moreover, it appears that low resting glycogen per se does not impair the increase in TCAI during moderate exercise.

scholarly journals Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations

2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Huiyuan Zhu ◽  
Dexi Bi ◽  
Youhua Zhang ◽  
Cheng Kong ◽  
Jiahao Du ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Therapeutic Potential ◽  
Ketone Bodies ◽  
Intractable Epilepsy ◽  
Mechanisms Of Action ◽  
Therapeutic Effects ◽  
Clinical Implementation ◽  
Research Attention ◽  
Low Carbohydrate Diet ◽  
Underlying Mechanisms

AbstractThe ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.

scholarly journals The effect of ketone bodies on alanine and glutamine metabolism in isolated skeletal muscle from the fasted chick

1988 ◽  
Vol 255 (1) ◽  
pp. 139-144 ◽  
Author(s):  
G Y Wu ◽  
J R Thompson
Keyword(s):  
Ketone Bodies ◽  
Intracellular Concentration ◽  
Glutamine Metabolism ◽  
Inhibiting Effect ◽  
Branched Chain Amino Acid ◽  
The Media ◽  
Inhibition Of Glycolysis ◽  
Alanine Synthesis ◽  
Branched Chain ◽  
Beta Hydroxybutyrate

The effects of ketone bodies on the metabolism of alanine and glutamine were studied in isolated extensor digitorum communis (EDC) muscles from 24 h-fasted chicks. (1) Acetoacetate and DL-beta-hydroxybutyrate (4 mM) markedly inhibit branched-chain amino acid (BCAA) transamination and alanine formation. (2) Ketone bodies (1 and 4 mM) increase the intracellular concentration and release of glutamate and glutamine, suggesting that inhibition of BCAA transamination does not limit intracellular availability of glutamate for alanine synthesis. (3) Ketone bodies (1 and 4 mM) do not affect glucose uptake by muscles, but decrease the rate of glycolysis as well as the intracellular concentration and release of pyruvate in muscles. (4) Addition of 12 mM-glucose increases the formation of alanine in muscles incubated in the absence of ketone bodies, but has no effect in muscles incubated in the presence of 4 mM ketone bodies. (5) Addition of 5 mM-pyruvate to the media prevents the inhibiting effect of ketone bodies on BCAA transamination and alanine synthesis. These results suggest that ketone bodies decrease alanine synthesis by limiting the intracellular availability of pyruvate, owing to inhibition of glycolysis, and inhibit BCAA transamination by decreasing the intracellular concentration of amino-group acceptors such as pyruvate in EDC muscles from fasted chicks.

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