Multiorgan Metabolomics and Lipidomics Provide New Insights Into Fat Infiltration in the Liver, Muscle Wasting, and Liver–Muscle Crosstalk Following Burn Injury

Abstract

Abstract Burn injury mediated hypermetabolic syndrome leads to increased mortality among severe burn victims, due to liver failure and muscle wasting. Metabolic changes may persist up to 2 years following the injury. Thus, understanding the underlying mechanisms of the pathology is crucially important to develop appropriate therapeutic approaches. We present detailed metabolomic and lipidomic analyses of the liver and muscle tissues in a rat model with a 30% body surface area burn injury located at the dorsal skin. Three hundred and thirty-eight of 1587 detected metabolites and lipids in the liver and 119 of 1504 in the muscle tissue exhibited statistically significant alterations. We observed excessive accumulation of triacylglycerols, decreased levels of S-adenosylmethionine, increased levels of glutamine and xenobiotics in the liver tissue. Additionally, the levels of gluconeogenesis, glycolysis, and tricarboxylic acid cycle metabolites are generally decreased in the liver. On the other hand, burn injury muscle tissue exhibits increased levels of acyl-carnitines, alpha-hydroxyisovalerate, ophthalmate, alpha-hydroxybutyrate, and decreased levels of reduced glutathione. The results of this preliminary study provide compelling observations that liver and muscle tissues undergo distinctly different changes during hypermetabolism, possibly reflecting liver–muscle crosstalk. The liver and muscle tissues might be exacerbating each other’s metabolic pathologies, via excessive utilization of certain metabolites produced by each other.