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.
Conflict of interest statement
The authors declare that they have no conflict of interest.
IL-6 Signal From the Bone Marrow Is Required for the Browning of White Adipose Tissue Post Burn InjuryA Abdullahi et al. Shock 47 (1), 33-39. PMID 27648696.The hypermetabolic stress response after burn contributes to multi-organ failure, sepsis, morbidity, and mortality. The cytokine interleukin 6 (IL-6) has been hypothesize …
Alternatively Activated Macrophages Drive Browning of White Adipose Tissue in BurnsA Abdullahi et al. Ann Surg 269 (3), 554-563. PMID 28817438.Together, our findings uncover macrophages as the key instigators and missing link in trauma-induced browning.
NLRP3 Inflammasome Mediates White Adipose Tissue Browning After BurnR Vinaik et al. Am J Physiol Endocrinol Metab 317 (5), E751-E759. PMID 31453709.A hallmark after burn is the stress and inflammatory-induced hypermetabolic response. Recently, we and others found that browning of white adipose tissue (WAT) is a criti …
Taming the Flames: Targeting White Adipose Tissue Browning in Hypermetabolic ConditionsA Abdullahi et al. Endocr Rev 38 (6), 538-549. PMID 28938469. - ReviewIn this era of increased obesity and diabetes prevalence, the browning of white adipose tissue (WAT) has emerged as a promising therapeutic target to induce weight loss a …
White Adipose Tissue Browning: A Double-edged SwordA Abdullahi et al. Trends Endocrinol Metab 27 (8), 542-552. PMID 27397607. - ReviewThe study of white adipose tissue (WAT) 'browning' has become a 'hot topic' in various acute and chronic metabolic conditions, based on the idea that WAT browning might b …
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