• Annals of surgery · Dec 2023

    Single-nuclei RNA Profiling Reveals Disruption of Adipokine and Inflammatory Signaling in Adipose Tissue of Burn Patients.

    • Carly M Knuth, Zachary Ricciuti, Dalia Barayan, Sarah Rehou, Abdikarim Abdullahi, Lauar de Brito Monteiro, and Marc G Jeschke.
    • Institute of Medical Science, University of Toronto, Toronto, Canada.
    • Ann. Surg. 2023 Dec 1; 278 (6): e1267e1276e1267-e1276.

    ObjectiveWe conducted a large-scale investigation of the systemic and adipose tissue-specific alterations in a clinical population of burn patients to identify factors that may influence hypermetabolism.BackgroundPrevious research has identified chronic disturbances in adipose tissue inflammation, lipolysis, and browning, which may drive the perpetuation of hypermetabolism following the severe adrenergic stress of a burn injury. Given that adipose tissue is thought to be a central node in the regulation of systemic metabolism, we believe that systematically delineating the pathologic role of adipose tissue postburn, will lead to the identification of novel interventions to mitigate morbidity and mortality from severe burns.MethodsThis was a single-institution cohort study, which obtained plasma and subcutaneous adipose tissue samples from severely burn adult patients over various time points during acute hospitalization. Whole-body clinical, metabolic, and inflammatory mediators were assessed in plasma, while genetic analyses through RT-qPCR and single-nuclei RNA sequencing were conducted in adipose tissue.ResultsSystemic inflammation and adrenergic stress increase IL-6 signaling, lipolysis, browning, and adipokine dysfunction in the adipose tissue of adult burn patients, which may further propagate the long-term hypermetabolic response. Moreover, using single-nuclei RNA sequencing, we provide the first comprehensive characterization of alterations in the adipose tissue microenvironment occurring at acute and chronic stages postburn.ConclusionWe provide novel insight toward the effect of burns on adipokine release, inflammatory signaling pathways, and adipose heterogeneity over the trajectory of acute and chronic stages.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

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