Figure 7

Increased WAT lipolysis and its hypothetical contribution to immunological and metabolic impairment in the two-hit model of burn plus LPS. In the acute phase after major trauma, such as an extensive burn, excessive DAMPs and PAMPs, which are derived from wounds, gut, homeostasis derangement and damaged tissues, redistribute to liver and WAT, induce ER stress and stimulate inflammasome activation in these tissues. ER stress and inflammasome activation in WAT contribute to apoptosis and lipolysis, releasing FFA and glycerol, which, subsequently, accumulate in the liver. Lipid deposition in the liver not only augments hepatic ER stress and impairs hepatic metabolic signaling but also inhibits LPS clearance and further stimulates the inflammasome, which perturbs hepatic immune function. In the two-hit model, LPS exacerbates impaired metabolism by stimulating both canonical WAT lipolysis and a proinflammatory response in the liver.