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

Deutz, Nicolaas E. P.; Singer, Pierre; Wierzchowska-McNew, Raven; Viana, Marina Verçoza; Bendavid, Itai; Pantet, Olivier; Thaden, John J.; Have, Gabriella A.M. Ten; Engelen, M.P.; Berger, Mette M.

doi:10.1016/j.metabol.2023.155400

Cited by 8 publications

(21 citation statements)

References 49 publications

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“…Both approaches give comparable differences between studied groups, albeit the absolute productions differ [15]. We recently introduced compartmental analysis of the decay curve of the studied groups [7 ▪ ]. The results as shown in the Figures and Tables are a recalculation with this approach of the results previously published [6 ▪ ] and now show whole body and intracellular productions of the difference between healthy and critically ill patients.…”

Section: How To Measure Amino Acid Kinetics?mentioning

confidence: 78%

“…Previously, the primed constant and continuous infusion approach was used in ICU studies with intravenous infusion of stable amino acid tracers using calibrated pumps [9–11]. This approach has some disadvantages as the measured production of several amino acids is often underestimated by 40–60% as the intracellular precursor pool production cannot be assessed [7 ▪ ]. We have, therefore, used compartmental analysis to estimate the actual intracellular production of amino acids (Tables 1 and 2).…”

Section: How To Measure Amino Acid Kinetics?mentioning

confidence: 99%

“…Protein breakdown and synthesis are generally increased in many organs of critically ill patients, leading to an overall increase in whole body amino acid kinetics [6 ▪ ,7 ▪ ,16 ▪▪ ]. This has been primarily explained by the enhanced amino acid flux from the muscle tissue (caused by severe muscle protein catabolism) to the liver in critical illness, leading to enhanced liver protein synthesis and disposal of amino acids into processes like gluconeogenesis and urea genesis.…”

Section: Why Is Amino Acid Production Changed In Critical Illness?mentioning

confidence: 99%

“…Open symbols are healthy, and closed symbols are the ICU patients. The results are compartmental reanalysis as described previously [6 ▪ ,7 ▪ ] and were 49 healthy subjects (27 male individuals, 22 female individuals) and 51 critically ill patients (36 male individuals and 15 female individuals). We did not measure alanine as there is a very large interchange with pyruvate and other amino acids.…”

Section: Why Is Amino Acid Production Changed In Critical Illness?mentioning

confidence: 99%

“…Whether these changes in the plasma concentrations actually represent changes in the production and/or disposal of these amino acids remains unclear and needs further exploration using stable isotope methodology. We recently showed that very weak relationships exist between plasma concentrations and kinetics of amino acids, except for amino acids that only have one disposal mechanism like tau-methylhistidine and hydroxyproline [6 ▪ ,7 ▪ ]. Therefore, to understand changes in metabolism of amino acids in the critically ill, it is required to take a different approach…”

Section: Introductionmentioning

confidence: 99%

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Amino acid kinetics in the critically ill

Deutz,

Haines,

Wischmeier

et al. 2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review Stable isotope methods have been used for many years to assess whole body protein and amino acid kinetics in critically ill patients. In recent years, new isotope approaches and tracer insights have been developed. The tracer pulse approach has some advantages above the established primed-continuous tracer infusion approach because of the high amount of metabolic information obtained, easy applicability, and low tracer costs. Effects of disease severity and sex on amino acid kinetics in ICU patients will also be addressed. Recent findings Current knowledge was synthesized on specific perturbations in amino acid metabolism in critically ill patients, employing novel methodologies such as the pulse tracer approach and computational modeling. Variations were evaluated in amino acid production and linked to severity of critical illness, as measured by SOFA score, and sex. Production of the branched-chain amino acids (BCAAs), glutamine, tau-methylhistidine and hydroxyproline were elevated in critical illness, likely related to increased transamination of the individual BCAAs or increased breakdown of proteins. Citrulline production was reduced, indicative of impaired gut mucosa function. Sex and disease severity independently influenced amino acid kinetics in ICU patients. Summary Novel tracer and computational approaches have been developed to simultaneously measure postabsorptive kinetics of multiple amino acids that can be used in critical illness. The collective findings lay the groundwork for targeted individualized nutritional strategies in ICU settings aimed at enhancing patient outcomes taking into account disease severity and sex.

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Section: How To Measure Amino Acid Kinetics?mentioning

confidence: 78%

Section: How To Measure Amino Acid Kinetics?mentioning

confidence: 99%

Section: Why Is Amino Acid Production Changed In Critical Illness?mentioning

confidence: 99%

Section: Why Is Amino Acid Production Changed In Critical Illness?mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Amino acid kinetics in the critically ill

Deutz,

Haines,

Wischmeier

et al. 2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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4-phenylbutyric acid improves sepsis-induced cardiac dysfunction by modulating amino acid metabolism and lipid metabolism via Comt/Ptgs2/Ppara

Zhou,

Zhu,

et al. 2024

Metabolomics

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Introduction Cardiac dysfunction after sepsis the most common and severe sepsis-related organ failure. The severity of cardiac damage in sepsis patients was positively associated to mortality. It is important to look for drugs targeting sepsis-induced cardiac damage. Our previous studies found that 4-phenylbutyric acid (PBA) was beneficial to septic shock by improving cardiovascular function and survival, while the specific mechanism is unclear. Objectives We aimed to explore the specific mechanism and PBA for protecting cardiac function in sepsis. Methods The cecal ligation and puncture-induced septic shock models were used to observe the therapeutic effects of PBA on myocardial contractility and the serum levels of cardiac troponin-T. The mechanisms of PBA against sepsis were explored by metabolomics and network pharmacology. Results The results showed that PBA alleviated the sepsis-induced cardiac damage. The metabolomics results showed that there were 28 metabolites involving in the therapeutic effects of PBA against sepsis. According to network pharmacology, 11 hub genes were found that were involved in lipid metabolism and amino acid transport following PBA treatment. The further integrated analysis focused on 7 key targets, including Comt, Slc6a4, Maoa, Ppara, Pparg, Ptgs2 and Trpv1, as well as their core metabolites and pathways. In an in vitro assay, PBA effectively inhibited sepsis-induced reductions in Comt, Ptgs2 and Ppara after sepsis. Conclusions PBA protects sepsis-induced cardiac injury by targeting Comt/Ptgs2/Ppara, which regulates amino acid metabolism and lipid metabolism. The study reveals the complicated mechanisms of PBA against sepsis.

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