![]() ![]() Results: At 7 days post-burn, adult liver bioenergetics were significantly higher than their sham counterparts, indicative that this group had entered the hypermetabolic period following trauma. Changes in levels of oxidized proteins, lipids and nitrosylated proteins were monitored, and serum levels of mitochondrial DNA were analyzed via PCR. Respirometry was performed on freshly isolated samples using a Seahorse XF96 analyzer, and these data were complemented by in-gel activity assays for complexes of the electron transport chain. At day 7, mice were sacrificed and livers were collected for functional mitochondrial studies. Select mice received daily intraperitoneal injections post-burn of metformin (100 mg/kg). ![]() Methods: Both 8 week (adult) and 50 week (elderly) old C57BL/6 mice received a 30% total body surface area dorsal (98☌ for 10 sec) and ventral (98☌ for 2 sec) scald burn. Here, we investigated mitochondrial bioenergetics in the livers of adult and elderly mice following a severe burn to characterize age-dependent differences and determine if metformin can provide benefits. We have recently demonstrated that in patients, metformin administration is equal to insulin in its ability to limit stress-induced hyperglycemia, yet the effects of this antidiabetic agent at the cellular level have not been explored. The elderly, in particular, are susceptible to poor outcomes after burns, due primarily to a scarcity of knowledge on the biomolecular effects of trauma in this population. Objectives: Severe burn injuries are characterized by alterations in mitochondrial dynamics which coincide with the ‘ebb’ and ‘flow’ phase of metabolic progression following trauma. ![]() 1Sunnybrook Health Sciences Centre, Toronto, Canada 2Ross Tilley Burn Centre, Toronto, Canada and 3University of Toronto, Toronto, Canada METFORMIN CORRECTS HEPATIC MITOCHONDRIAL ABNORMALITIES IN A MURINE MODEL OF THERMAL TRAUMA Christopher Auger 1,2, Thibacg Sivayoganathan 1,2,3, Abdikarim Abdullahi 1,2,3, Alexandra Parousis 1,2 and Marc G. Still, there remains potential to monitor the immunometabolic state over time and intervene with immune- and metabolic-targeted therapies as novel therapeutic approaches in sepsis. However, the factors that drive mitochondrial changes and the role by which mitochondrial energy metabolism regulates immune cell functions during the host response to infection remain unclear. Our data suggests that decreased mitochondrial content leads to a reduction in mitochondrial respiration. ![]() Changes in mitochondrial energy metabolism are evident within leukocyte subsets in sepsis, suggesting that metabolic processes could be a novel therapeutic target. Within individual patients, a differential balance in these immune components can produce either a hyperinflammatory or an immunoparalytic phenotype. The acute phase of sepsis is driven by a strong immune response with both pro- and anti-inflammatory components. 1Children's Hospital of Philadelphia, Philadelphia, PA 2Center for Mitochondrial and Epigenomic Medicine, Philadelphia, PA and 3University of Pennsylvania Perelman School of Medicine, Philadelphia, PA MITOCHONDRIAL ENERGY METABOLISM AND THE IMMUNE RESPONSE IN SEPSIS Scott L. ![]()
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