The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs.

Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine model of sepsis, we explored the across organ net fluxes of gluconeogenic substrates.

Functional and metabolic effects of omega-3 polyunsaturated fatty acid supplementation and the role of β-hydroxy-β-methylbutyrate addition in chronic obstructive pulmonary disease: A randomized clinical trial.

Introduction: Short-term (4 weeks) supplementation with n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has recently been shown to improve protein metabolism in a dose dependent way in normal weight patients with Chronic Obstructive Pulmonary Disease (COPD). Furthermore, EPA/DHA supplementation was able to increase extremity lean soft tissue but not muscle function. No studies are available combining n-3 PUFAs and the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) supplementation in chronic clinical conditions.

Females have a different metabolic response to critical illness, measured by comprehensive amino acid flux analysis.

Background: The trajectory from healthy to critical illness is influenced by numerous factors, including metabolism, which differs substantially between males and females. Whole body protein breakdown is substantially increased in critically ill patients, but it remains unclear whether there are sex differences that could explain the different health outcomes. Hence, we performed a secondary analysis of a study, where we used a novel pulse isotope method in critically ill and matched healthy males and females.

Short-chain fatty acid production in accessible and inaccessible body pools as assessed by novel stable tracer pulse approach is reduced by aging independent of presence of COPD.

Background: Production rates of the short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which are beneficial metabolites of the intestinal microbiota, are difficult to measure in humans due to inaccessibility of the intestine to perform measurements, and the high first-pass metabolism of SCFAs in colonocytes and liver. We developed a stable tracer pulse approach to estimate SCFA whole-body production (WBP) in the accessible pool representing the systemic circulation and interstitial fluid. Compartmental modeling of plasma enrichment data allowed us to additionally calculate SCFA kinetics and pool sizes in the inaccessible pool likely representing the intestine with microbiota.

Obesity- and sex-related metabolism of arginine and nitric oxide in adults.

Background: There is growing interest in the supplementation of arginine (Arg) and citrulline (Cit) in obesity due to their potential anti-obesogenic and anti-inflammatory properties. However, there is no consensus on the metabolic changes in Arg kinetics in obesity.

Objectives: This exploratory cross-sectional study aimed to investigate the association between obesity, sex, and sex-by-obesity interaction on whole-body Arg kinetics in a large group of human subjects.

Impact of β-hydroxy-β-methylbutyrate (HMB) on muscle loss and protein metabolism in critically ill patients: A RCT.

Purpose: Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine, can attenuate this process.

Comprehensive metabolic amino acid flux analysis in critically ill patients.

Amino acid (AA) metabolism is severely disturbed in critically ill ICU patients. To be able to make a more scientifically based decision on the type of protein or AA nutrition to deliver in ICU patients, comprehensive AA phenotyping with measurements of plasma concentrations and whole body production (WBP) is needed. Therefore, we studied ICU patients and matched control subjects using a novel pulse isotope method to obtain in-depth metabolic analysis.

Correction: Protein fractional synthesis rates within tissues of high- and low-active mice.

[This corrects the article DOI: 10.1371/journal.pone.

Protein fractional synthesis rates within tissues of high- and low-active mice.

With the rise in physical inactivity and its related diseases, it is necessary to understand the mechanisms involved in physical activity regulation. Biological factors regulating physical activity are studied to establish a possible target for improving the physical activity level. However, little is known about the role metabolism plays in physical activity regulation.

Metabolic Consequences of Supplemented Methionine in a Clinical Context.

The central position of methionine (Met) in protein metabolism indicates the importance of this essential amino acid for growth and maintenance of lean body mass. Therefore, Met might be a tempting candidate for supplementation. However, because Met is also the precursor of homocysteine (Hcy), a deficient intake of B vitamins or excessive intake of Met may result in hyperhomocysteinemia (HHcy), which is a risk factor for cardiovascular disease.

Activated whole-body arginine pathway in high-active mice.

Our previous studies suggest that physical activity (PA) levels are potentially regulated by endogenous metabolic mechanisms such as the vasodilatory roles of nitric oxide (NO) production via the precursor arginine (ARG) and ARG-related pathways. We assessed ARG metabolism and its precursors [citrulline (CIT), glutamine (GLN), glutamate (GLU), ornithine (ORN), and phenylalanine (PHE)] by measuring plasma concentration, whole-body production (WBP), de novo ARG and NO production, and clearance rates in previously classified low-active (LA) or high-active (HA) mice. We assessed LA (n = 23) and HA (n = 20) male mice by administering a stable isotope tracer pulse via jugular catheterization.

Comprehensive metabolic flux analysis to explain skeletal muscle weakness in COPD.

Background & Aims: Metabolic characterization of a well-defined group of patients could be a powerful tool in revealing metabolic signatures to explain limb muscle weakness in chronic diseases. Studies are currently limited in Chronic Obstructive Pulmonary Disease (COPD) to the identification of differential amino acid concentrations but lack comprehensive analysis of the flux through relevant muscle function related metabolic pathways.

Methods: In 23 stable patients with moderate to very severe COPD and 19 healthy controls, a comprehensive metabolic flux analysis was conducted by administering an intravenous pulse and primed constant infusion of multiple stable tracers of amino acids known to play a role in muscle health.

New advances in stable tracer methods to assess whole-body protein and amino acid metabolism.

Purpose Of Review: Stable isotope methods have been used for many years to assess whole-body protein and amino acid kinetics in healthy conditions and in response to aging, exercise and (clinically stable) disease states.

Recent Findings: In recent years, tracer research expanded to the anabolic response to feeding in critical illness and its use during acute metabolic stressors. Furthermore, new isotope approaches and tracer insights have been obtained.

Metabolic phenotyping using kinetic measurements in young and older healthy adults.

Background: The aging process is often associated with the presence of sarcopenia. Although changes in the plasma concentration of several amino acids have been observed in older adults, it remains unclear whether these changes are related to disturbances in whole body production and/or interconversions.

Methods: We studied 10 healthy young (~22.

Determination of β-hydroxy-β-methylbutyrate concentration and enrichment in human plasma using chemical ionization gas chromatography tandem mass spectrometry.

Our objective was to develop a quick and simplified method for the determination of β-Hydroxy-β-methylbutyrate (HMB) and ɑ-ketoisocaproic acid (KIC) concentrations and enrichments by GC/MS/MS to determine the turnover rate of HMB in humans. In experiment 1, we provided a pulse of L-[5,5,5-H]leucine to younger adults in the postabsorptive state then collected blood samples over a 4h time period. In experiment 2, we provided a pulse of [3,4,methyl-C]HMB to older adults in the postabsorptive state then collected blood samples over a 3h time period.

Application of gas chromatography-tandem mass spectrometry (GC/MS/MS) for the analysis of deuterium enrichment of water.

Incorporation of deuterium from deuterium oxide ((2) H2 O) into biological components is a commonly used approach in metabolic studies. Determining the dilution of deuterium in the body water (BW) pool can be used to estimate body composition. We describe three sensitive GC/MS/MS methods to measure water enrichment in BW.

A narrow quantitative trait locus in C. elegans coordinately affects longevity, thermotolerance, and resistance to paraquat.

By linkage mapping of quantitative trait loci, we previously identified at least 11 natural genetic variants that significantly modulate Caenorhabditis elegans life-span (LS), many of which would have eluded discovery by knock-down or mutation screens. A region on chromosome IV between markers stP13 and stP35 had striking effects on longevity in three inter-strain crosses (each P < 10(-9)). In order to define the limits of that interval, we have now constructed two independent lines by marker-based selection during 20 backcross generations, isolating the stP13-stP35 interval from strain Bergerac-BO in a CL2a background.

Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants.

Many lifespan-modulating genes are involved in either generation of oxidative substrates and end-products, or their detoxification and removal. Among such metabolites, only lipoperoxides have the ability to produce free-radical chain reactions. For this study, fatty-acid profiles were compared across a panel of C.

An iterative block-shifting approach to retention time alignment that preserves the shape and area of gas chromatography-mass spectrometry peaks.

Background: Metabolomics, petroleum and biodiesel chemistry, biomarker discovery, and other fields which rely on high-resolution profiling of complex chemical mixtures generate datasets which contain millions of detector intensity readings, each uniquely addressed along dimensions of time (e.g., retention time of chemicals on a chromatographic column), a spectral value (e.

Remarkable longevity and stress resistance of nematode PI3K-null mutants.

The great majority of lifespan-augmenting mutations were discovered in the nematode Caenorhabditis elegans. In particular, genetic disruption of insulin-like signaling extends longevity 1.5- to 3-fold in the nematode, and to lesser degrees in other taxa, including fruit flies and mice.

Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI).

There is a general consensus that supports the need for standardized reporting of metadata or information describing large-scale metabolomics and other functional genomics data sets. Reporting of standard metadata provides a biological and empirical context for the data, facilitates experimental replication, and enables the re-interrogation and comparison of data by others. Accordingly, the Metabolomics Standards Initiative is building a general consensus concerning the minimum reporting standards for metabolomics experiments of which the Chemical Analysis Working Group (CAWG) is a member of this community effort.

Mutagenic effects of 4-hydroxynonenal triacetate, a chemically protected form of the lipid peroxidation product 4-hydroxynonenal, as assayed in L5178Y/Tk+/- mouse lymphoma cells.

The lipid peroxidation product 4-hydroxynon-2-enal (4-HNE) is cytotoxic and genotoxic at superphysiological concentrations. To characterize the mechanism of action of 4-HNE, we assessed genotoxic damage by 4-HNE and by 4-HNE triacetate [4-HNE(Ac)(3)] using the mouse lymphoma assay that measures the mutant frequency in the Tk gene. As a strong electrophile, 4-HNE reacts readily with nucleophilic centers on cellular components.

Genetic loci modulating fitness and life span in Caenorhabditis elegans: categorical trait interval mapping in CL2a x Bergerac-BO recombinant-inbred worms.

Quantitative trait loci (QTL) can implicate an unbiased sampling of genes underlying a complex, polygenic phenotype. QTL affecting longevity in Caenorhabditis elegans were mapped using a CL2a x Bergerac-BO recombinant-inbred population. Genotypes were compared at 30 transposon-specific markers for two paired sample sets totaling 171 young controls and 172 longevity-selected worms (the last-surviving 1%) from a synchronously aged population.