Burn-associated metabolic dysfunction: could extracellular vesicles play a role?

Hypermetabolism is a well-recognized component of the detrimental systemic response following severe burn injury. Despite extensive clinical observations and research output, the underlying mechanisms that drive this persistent metabolic dysregulation remain poorly understood. One emerging area of interest is the role of extracellular vesicles (EVs), small membrane-bound particles released by cells that are increasingly recognized as important mediators of intercellular communication and contributors to various pathological conditions. Recent studies have highlighted their significant involvement in metabolic regulation, acting as carriers of bioactive molecules that influence metabolic pathways in recipient cells. EVs contribute to the modulation of glucose and lipid metabolism, insulin sensitivity, mitochondrial function, and inflammation, thereby influencing systemic metabolic homeostasis. In this context, EVs have been proposed as potential mediators in the metabolic problems that follow severe burn injuries. Burn-induced hypermetabolism, marked by insulin resistance, muscle wasting, and systemic inflammation, is affected by exosome-driven signaling between damaged tissues and metabolic organs. Exosomes released after a burn carry inflammatory cytokines, stress-response proteins, and metabolic regulators that change cellular functions in distant organs such as the liver, skeletal muscle, and adipose tissue. Understanding how exosomal communication contributes to post-burn metabolic issues could lead to new diagnostic and treatment options for improving recovery and metabolic health in burn patients. This review aims to clarify the role of EVs in burn-induced metabolic problems, emphasizing their potential as new mediators in the complex systemic response, which may provide new insights into the underlying mechanisms and help identify novel therapeutic targets.