Bone Marrow-Derived Mesenchymal Stem Cells Alleviate Hepatic Lipid Metabolism Disorders After Scald Injury: Integrating Liver Transcriptome and Metabolome

Abstract

Previous studies have confirmed that scald injuries can lead to disturbances in hepatic lipid metabolism, and bone marrow-derived mesenchymal stem cells (BMSCs) have emerged as a promising therapeutic strategy for alleviating such disorders. However, research focusing on the regulation and restoration of liver lipid metabolic processes remains limited. In this study, we investigated the effects of BMSCs on hepatic lipid metabolism disorders induced by scald injury in rats through integrated transcriptomic and metabolomic analyses. The results demonstrated that portal vein infusion of BMSCs markedly improved body weight recovery, reduced hepatic lipid accumulation, normalized serum lipid profiles, and attenuated liver injury following scalding. Combined transcriptomic and metabolomic data further suggested that the therapeutic mechanism may involve inhibition of NF-κB/Gadd45a signaling in hepatocytes, restoration of sphingolipid metabolism, enhancement of hepatic lipid conversion, and suppression of adipocyte lipolysis. Overall, this study provides a theoretical basis for the potential clinical application of BMSCs in treating hepatic lipid metabolism disorders secondary to severe burn injury.

1. Introduction

It is estimated that the annual incidence of burns and scalds in the United States exceeds 2 million, with approximately 3400 individuals dying from scald-related injuries each year. The financial burden associated with the treatment of burn and scald patients is estimated to exceed 573 million USD annually [1, 2]. Among these injuries, thermal burns and scalds together account for more than 90% of all cases, and systemic complications arising from such injuries lead to approximately 250,000 deaths worldwide each year [3]. This high mortality rate is largely attributed to profound metabolic disturbances—including systemic inflammation, negative nitrogen balance, elevated resting energy expenditure, and altered glucose and lipid metabolism—which commonly occur following severe thermal injury [4–7]. These pathological changes can ultimately result in multiple organ dysfunction syndrome (MODS) and death [8–10]. Therefore, elucidating the organ-specific responses following scald injury is of great importance, as it may contribute to the development of targeted therapeutic strategies and improve patient prognosis.

The liver is one of the primary organs affected by scald injury, exhibiting marked morphological alterations such as hepatomegaly and lipid infiltration [11, 12]. Given its central role in regulating systemic metabolic functions under both physiological and stress conditions, it is critical to address hepatic metabolic disturbances that occur following scald injury. In our preliminary experiments, we confirmed that severe cutaneous scalds induce hepatic steatosis, which is associated with multiple factors, including peripheral lipolysis, impaired hepatic function, and infiltration of inflammatory cells [13]. Moreover, our findings revealed that hepatic steatosis progressively worsens during the first seven days after scald injury, consistent with the dynamic changes in serum AST and ALT levels observed in clinical burn patients [14]. However, to date, there have been no specific therapeutic interventions or detailed studies focusing on the treatment of scald-induced hepatic steatosis.