74 Adipose Tissue from Burn Patients is Proinflammatory, Lipolytic and a Key Initiator of Hepatic Dysfunction

Abstract

Severe burns induce systemic dysfunction characterized by chronic increased resting energy expenditure, catabolism of fat and muscle tissues, hepatomegaly and liver damage. The role of adipose tissue in initiating these complications has not been adequately defined. The aims of this study were to characterize the adipose tissue secretome of burn patients and delineate the extent of damage these biomolecules exert on hepatocytes compared to healthy control adipose. White adipose tissue (WAT) from burn patients admitted to a local burn centre requiring surgery and healthy controls undergoing elective procedures were used to prepare explant cultures. Gas chromatography-mass spectrometry and cytokine arrays were applied to characterize samples. These were subsequently incubated with human hepatocytes (HepG2) to elucidate their effects on cellular function. Seahorse XF96 analysis was used to study mitochondrial dynamics, and expression of endoplasmic reticulum (ER) stress and apoptosis markers were probed. Here, we show that WAT from burn patients undergoes extensive lipolysis and the release of inflammatory mediators compared to healthy control tissue. Treatment of hepatocytes with burned adipose explant media significantly raised ER stress and apoptosis markers while increasing mitochondrial oxygen uptake and inducing UCP2-mediated uncoupling (p ≤ 0.05). Further, the adipose secretome of burn patients alters nutrient homeostasis and mitophagy in hepatocytes, as indicated by the phosphorylation of acetyl-CoA carboxylase (Ser 79) and changes to mTORC1 and PINK1 expression. The adipose tissue, generally regarded as a mere storage depot, is often overlooked as a contributor to systemic dysfunction post-trauma. Our results single out the adipose secretome of burn patients as an inducer of hepatocellular ER stress, mitochondrial hyperfusion/uncoupling and ultimately, cell death. The data herein indicate that the adipose tissue acts as an initiator of systemic alterations following burn. Therapeutic interventions which reverse these morphological changes to WAT may be beneficial in reducing systemic complications.