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

Ann Surg. 2023 Apr 14. doi: 10.1097/SLA.0000000000005880. Online ahead of print.


Objective: We 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.

Background: Previous 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. Give that adipose tissue is thought to be a central node in the regulation of systemic metabolism, we believe that by systematically delineating the pathological role of adipose tissue post-burn, this will lead to the identification of novel interventions to mitigate morbidity and mortality from severe burns.

Methods: This was a single-institution cohort study, which obtained plasma and subcutaneous adipose tissue samples from severely burn adult patients over various timepoints during acute hospitalization. Whole-body clinical, metabolic, and inflammatory mediators were assessed in plasma, while genetic analyses via RT-qPCR and single-nuclei RNA sequencing (snRNA-seq) were conducted in adipose tissue.

Results: Systemic inflammation and adrenergic stress increases 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 snRNA-seq, we provide the first comprehensive characterization of alterations in the adipose tissue microenvironment occurring at acute and chronic stages post-burn.

Conclusion: We provide novel insight towards the effect of burns on adipokine release, inflammatory signaling pathways, and adipose heterogeneity over the trajectory of acute and chronic stages.