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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 \u201ccross-talk\u201d between the adipose and liver tissue in the context of burn injury, which is critically mediated by WAT browning.<\/jats:p>","DOI":"10.1038\/s41419-019-2103-2","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T10:01:37Z","timestamp":1574071297000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction"],"prefix":"10.1038","volume":"10","author":[{"given":"Abdikarim","family":"Abdullahi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osai","family":"Samadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Auger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharsan","family":"Kanagalingam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Boehning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0870-1664","authenticated-orcid":false,"given":"Marc G.","family":"Jeschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,18]]},"reference":[{"key":"2103_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021245","volume":"6","author":"MG Jeschke","year":"2011","unstructured":"Jeschke, M. 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