ArticleMetabolomics : Official journal of the Metabolomic Society2024
Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.
Article in Metabolomics : Official journal of the Metabolomic Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 26 citations in OpenAlex.
- Longitudinal multiomic signatures of ARDS and sepsis inflammatory phenotypes identify pathways associated with mortality.The Journal of clinical investigation · 2026Trial
- Comorbidities and Inflammation: How Chronic Diseases Prime the Host Response in Sepsis.International journal of molecular sciences · 2026Review
- Metabolomics ofbioRxiv : the preprint server for biology · 2026Article
- Lactate as a Chemical Modification on Proteins and Metabolites.Annual review of biochemistry · 2026Review
- N-terminal formylmethionine as a degron and a specific signal in proteostasis and stress adaptation.Experimental & molecular medicine · 2026Review
- The Emerging Role of N-Lactoyl-Phenylalanine (Lac-Phe) in Metabolic Regulation and Disease: From Exercise-Induced Metabolite to Therapeutic Candidate.Antioxidants (Basel, Switzerland) · 2026Article
- Untargeted Metabolomics Identifies N-Lactoyl-Amino Acids as Dose-Responsive Plasma Biomarkers of Metformin Adherence in Type 2 Diabetes.Clinical pharmacology and therapeutics · 2026Article
- 4,5-dihydroxyhexanoic acid is a robust circulating and urine marker of mitochondrial disease and its severity.bioRxiv : the preprint server for biology · 2026Article
- Sepsis and the immunometabolic inflammatory response.npj metabolic health and disease · 2026Review
- Plasma Metabolites Associated with CKD Stage in Autosomal Dominant Tubulointerstitial Kidney Disease.Kidney360 · 2026Article
- Beyond exercise and appetite: The expanding biology and therapeutic potential of N-lactoyl-phenylalanine.The Journal of pharmacology and experimental therapeutics · 2026Review
- Lac-Phe: An Emerging Appetite-Regulating Exerkine with Health and Therapeutic Benefits.Current obesity reports · 2026Review
- Reversible Secondary Carnitine Deficiency Associated With ChronicClinical medicine insights. Case reports · 2026Article
- N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis.Human molecular genetics · 2025Article
- Lac-Phe induces hypophagia by inhibiting AgRP neurons in mice.Nature metabolism · 2025Article
- Lac-Phe: a central metabolic regulator and biomarker.Medical review (2021) · 2025Article
- N-lactoyl amino acids are potential biomarkers for insulin resistance and diabetic complications.Diabetes, obesity & metabolism · 2025Article
- Longitudinal multi-omic signatures of ARDS and sepsis inflammatory phenotypes identify key pathways associated with mortality.medRxiv : the preprint server for health sciences · 2025Article
- Article
- N-Lactoyl Amino Acids: Emerging Biomarkers in Metabolism and Disease.Diabetes/metabolism research and reviews · 2025Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
introductionSepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.
objectiveTo assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.
methodsWe performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.
resultsNine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.
conclusionFuture studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.