Hepatic steatosis associated with decreased β-oxidation and mitochondrial function contributes to cell damage in obese mice after thermal injury

Severely burned patients who are morbidly obese have poor clinical outcomes with aggravated metabolic consequences, a higher incidence of multiple organ dysfunction/failure, and significantly increased morbidity and mortality. The underlying mechanisms of these adverse outcomes are essentially unknown. Since the liver is one of the central metabolic organs, we hypothesized that thermal injury in obese patients leads to substantially increased lipolysis, hepatic fat infiltration, resulting in profound hepatic cellular and organellar alterations, consequently causing liver damage and severely augmented metabolic dysfunction. We tested this hypothesis using an obese mouse model subjected to a 20% total body surface area burn injury. C57BL/6 mice were randomly divided into low-fat diet (LFD) and high-fat diet (HFD) sham and burn groups (n = 6 per group) and fed for 16 weeks. 7 days after the thermal injury portal and cardiac blood were taken separately and liver tissue was collected for western blotting and immunohistochemical analysis. Gross examination of the liver showed apparent lipid infiltration in HFD fed and burned mice. We confirmed that augmented ER stress and inhibition of Akt-mTOR signaling dysregulated calcium homeostasis, contributed to the decrease of ER–mitochondria contact, and reduced mitochondrial β-oxidation in HFD fed and burned mice, leading to profound hepatic fat infiltration and substantial liver damage, hence increased morbidity and mortality. We conclude that obesity contributes to hepatic fat infiltration by suppressing β-oxidation, inducing cell damage and subsequent organ dysfunction after injury.