Search results for " Branched-Chain"
showing 10 items of 10 documents
Decreased consumption of branched-chain amino acids improves metabolic health
2016
Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino…
Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED Trial
2016
Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential conf…
Chronically elevated branched chain amino acid levels are pro-arrhythmic.
2022
Aim. Cardiac arrhythmias comprise a major health and economic burden and are associated with significant morbidity and mortality, including cardiac failure, stroke and sudden cardiac death (SCD). Development of efficient preventive and therapeutic strategies is hampered by incomplete knowledge of disease mechanisms and pathways. Our aim is to identify novel mechanisms underlying cardiac arrhythmia and SCD using an unbiased approach. Methods and Results. We employed a phenotype-driven N-ethyl-N-nitrosourea (ENU) mutagenesis screen and identified a mouse line with a high incidence of sudden death at young age (6-9 weeks) in the absence of prior symptoms. Affected mice were found to be homozyg…
Higher glucose availability augments the metabolic responses of the C2C12 myotubes to exercise-like electrical pulse stimulation
2021
The application of exercise-like electrical pulse simulation (EL-EPS) has become a widely used exercise mimetic in vitro. EL-EPS produces similar physiological responses as in vivo exercise, while less is known about the detailed metabolic effects. Routinely, the C2C12 myotubes are cultured in high-glucose medium (4.5 g/L), which may alter EL-EPS responses. In this study, we evaluate the metabolic effects of EL-EPS under the high- and low-glucose (1.0 g/L) conditions to understand how substrate availability affects the myotube response to EL-EPS. The C2C12 myotube, media, and cell-free media metabolites were analyzed using untargeted nuclear magnetic resonance (NMR)-based metabolomics. Furt…
Branched-Chain and Aromatic Amino Acids Are Associated With Insulin Resistance During Pubertal Development in Girls.
2018
Cross-sectional studies in children show branched-chain and aromatic amino acids are associated with insulin resistance, but whether these associations persist from childhood to adulthood is not known. This study aimed to assess whether circulating amino acids associate with insulin resistance during pubertal development.This was a 7.5-year longitudinal study from childhood to early adulthood. A total of 396 nondiabetic Finnish girls aged 11.2 ± .8 years at baseline participated in the study which was conducted at the Health Science Laboratory, University of Jyväskylä. Serum concentrations of glucose and insulin were determined by enzymatic photometric methods and amino acids by nuclear mag…
Diastolic left ventricular function in relation to circulating metabolic biomarkers in a population study
2019
AimsWe studied the association of circulating metabolic biomarkers with asymptomatic left ventricular diastolic dysfunction, a risk-carrying condition that affects 25% of the population.Methods and resultsIn 570 randomly recruited people, we assessed in 2005–2010 and in 2009–2013 the multivariable-adjusted correlations of e’ (early left ventricular relaxation) and E/e’ (left ventricular filling pressure) measured by Doppler echocardiography with 43 serum metabolites, quantified by magnetic resonance spectroscopy. In 2009–2013, e’ cross-sectionally increased (Bonferroni corrected p ≤ 0.016) with the branched-chain amino acid valine (per one standard deviation increment, +0.274 cm/s (95% conf…
ITCH E3 ubiquitin ligase downregulation compromises hepatic degradation of branched-chain amino acids
2022
Objective: Metabolic syndrome, obesity, and steatosis are characterized by a range of dysregulations including defects in ubiquitin ligase tagging proteins for degradation. The identification of novel hepatic genes associated with fatty liver disease and metabolic dysregulation may be relevant to unravelling new mechanisms involved in liver disease progression Methods: Through integrative analysis of liver transcriptomic and metabolomic obtained from obese subjects with steatosis, we identified itchy E ubiquitin protein ligase (ITCH) as a gene downregulated in human hepatic tissue in relation to steatosis grade. Wild-type or ITCH knockout mouse models of non-alcoholic fatty liver disease (N…
Cloning of branched chain amino acid biosynthesis genes and assays of alpha-acetolactate synthase activities in Leuconostoc mesenteroides subsp. crem…
1999
Abstract A genomic library from Leuconostoc mesenteroides subsp. cremoris (Lmc) in Escherichia coli was screened for α-acetolactate synthase (ALS) activity using a phenotypic test detecting the production of acetolactate or related C 4 derivatives (diacetyl, acetoin or 2,3-butanediol) in the culture. Four recombinant E. coli clones, with plasmids containing overlapping DNA fragments and displaying anabolic ALS activity, were selected. This activity is encoded by an ilvB gene belonging to a putative operon which contains genes highly similar to the genes of the branched chain amino acid (BCAA) operon of Lactococcus lactis subsp. lactis. This putative BCAA operon is not functional as the ilvA…
Influence of N-acetylcysteine on hepatic amino acid metabolism in patients undergoing orthotopic liver transplantation
2001
Experimental treatment with the antioxidant and glutathione precursor N-acetylcysteine (NAC) has been performed in orthotopic liver transplantation (OLT) to reduce reperfusion injury. To investigate the effect of NAC on the hepatic and intestinal amino acid metabolism, intraoperative amino acid exchange rates were studied in liver transplant recipients with high dose NAC treatment (n = 10) and in control patients (n = 9). Treatment with NAC was found to cause a loss of amino acids and increased urea nitrogen release from the liver graft. The net balance of most amino acids was shifted to increased hepatic release or decreased hepatic uptake. The initial cumulative splanchnic release of all …
Potential role of branched-chain amino acid catabolism in regulating fat oxidation.
2013
Insulin-resistant or obese individuals have increased serum branched-chain amino acid (BCAA) levels. Recent findings relate increased BCAA catabolism to increased fatty acid oxidation and better metabolic health in physically active individuals. We hypothesize that, via glyceroneogenesis, BCAA catabolism mediates increased constitutive use of fatty acids for β-oxidation in subjects with increased inherent or acquired aerobic capacity both during exercise and at rest.