Dynamic changes in the mouse hepatic lipidome following warm ischemia reperfusion injury

Abstract

Liver failure secondary to nonalcoholic fatty liver disease (NAFLD) has become the most common cause for liver transplantation in many parts of the world. Moreover, the prevalence of NAFLD not only increases the demand for liver transplantation, but also limits the supply of suitable donor organs because steatosis predisposes grafts to ischemia-reperfusion injury (IRI). There are currently no pharmacological interventions to limit hepatic IR injury because the mechanisms by which steatosis leads to increased injury are unclear. To identify potential novel mediators of IR injury, we used liquid chromatography and mass spectrometry to assess temporal changes in the hepatic lipidome in steatotic and non-steatotic livers after warm IRI in mice. Our untargeted analyses revealed distinct differences between the steatotic and non-steatotic response to IRI and highlighted dynamic changes in lipid composition with marked changes in glycerolipids and glycerophospholipids. These findings enhance our knowledge of the lipidomic changes that occur following IRI and provide a foundation for future mechanistic studies. A better understanding of the mechanisms underlying such changes will lead to novel therapeutic strategies to combat IR injury.