Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction

Abdikarim Abdullahi, Osai Samadi, Christopher Auger, Tharsan Kanagalingam, Darren Boehning, Sheng Bi, Marc G. Jeschke

Research output: Contribution to journalArticle

Abstract

Burn patients experiencing hypermetabolism develop hepatic steatosis, which is associated with liver failure and poor outcomes after the injury. These same patients also undergo white adipose tissue (WAT) browning, which has been implicated in mediating post-burn cachexia and sustained hypermetabolism. Despite the clinical presentation of hepatic steatosis and WAT browning in burns, whether or not these two pathological responses are linked remains poorly understood. Here, we show that the burn-induced WAT browning and its associated increased lipolysis leads to the accelerated development of hepatic steatosis in mice. Deletion of interleukin 6 (IL-6) and the uncoupling protein 1 (UCP1), regulators of burn-induced WAT browning completely protected mice from hepatic steatosis after the injury. Treatment of post-burn mice with propranolol or IL-6 receptor blocker attenuated burn-induced WAT browning and its associated hepatic steatosis pathology. Lipidomic profiling in the plasma of post-burn mice and burn patients revealed elevated levels of damage-inducing lipids (palmitic and stearic acids), which induced hepatic endoplasmic reticulum (ER) stress and compromised hepatic fat oxidation. Mechanistically, we show that hepatic ER stress after a burn injury leads to a greater ER-mitochondria interaction, hepatocyte apoptosis, oxidative stress, and impaired fat oxidation. Collectively, our findings uncover an adverse “cross-talk” between the adipose and liver tissue in the context of burn injury, which is critically mediated by WAT browning.

Original languageEnglish (US)
Article number870
JournalCell Death and Disease
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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    Abdullahi, A., Samadi, O., Auger, C., Kanagalingam, T., Boehning, D., Bi, S., & Jeschke, M. G. (2019). Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction. Cell Death and Disease, 10(12), [870]. https://doi.org/10.1038/s41419-019-2103-2