Severe Burn Injury Induces Thermogenically Functional Mitochondria in Murine White Adipose Tissue

Abstract

Chronic cold exposure induces functionally thermogenic mitochondria in the inguinal white adipose tissue (iWAT) of mice. Whether this response occurs in pathophysiological states remains unclear. The purpose of this study was to determine the impact of severe burn trauma on iWAT mitochondrial function in mice. Male balb-c mice (10–12 weeks) received full-thickness scald burns to ~30% of the body surface area. iWAT was harvested from mice at 1, 4, 10, 20, and 40 days post injury. Total and uncoupling protein 1 (UCP1) dependent mitochondrial thermogenesis were determined in iWAT. Citrate synthase (CS) activity was determined as a proxy of mitochondria abundance. Immunohistochemistry was performed to assess iWAT morphology and UCP1 expression. UCP1 dependent respiration was significantly greater at 4 and 10 days post burn compared to sham, peaking at 20 days post burn (P<0.001). CS activity was 3-fold greater at 4, 10, 20 and 40 days post-burn versus sham (P<0.05). Per mitochondrion, UCP1 function increased after burn trauma (P<0.05). After burn trauma, iWAT exhibited numerous multilocular lipid droplets which stained positive for UCP1. The current findings demonstrate the induction of thermogenically competent mitochondria within rodent iWAT in a model of severe burn trauma. These data identify a specific pathology which induces the browning of WAT in vivo, and may offer a mechanistic explanation for the chronic hypermetabolism observed in burn victims.

Browning of Subcutaneous White Adipose Tissue in Humans after Severe Adrenergic Stress

“…B panels i–vi), suggesting progressive browning of sWAT in response to burn trauma. This is in line with our findings in rodents, showing a gradual change in sWAT morphology after burn injury (Porter et al, 2015). Finally, transmission electron microscopy confirmed the presence of adipocytes with an abundance of small (0.5–1μm) lipid droplets and numerous electron-dense, rod-shaped mitochondria in the sWAT from burn patients (Fig.…”

“…3B). We found that CS activity significantly increased by 130% (38±11 vs. 89±16 nmol/g/sec) in the two weeks that patients were followed (P<0.01), which is agreement with our recent data showing greater CS activity in sWAT of burned mice (Porter et al, 2015). In addition to our morphological data (Fig 1C), these data provide further evidence that mitochondrial biogenesis occurs in sWAT following burn injury, similar to that which occurs in murine sWAT in response to chronic cold exposure (Shabalina et al, 2013).…”

“…3D), suggesting that each mitochondrion has a greater intrinsic capacity for leak respiration in the late burn group. These data are similar to our recent findings in burned mice, where sWAT respiratory capacity increase after injury, in addition to a shift in mitochondrial coupling control toward a more thermogenic phenotype (Porter et al, 2015). In pediatric patients followed prospectively after injury, leak respiration increased post injury (0.52±0.07 vs. 1.46±0.19 pmol/sec/mg) (Fig.…”

“…Moreover, expression of UCP1 mRNA acutely increases in the sWAT of burned rodents (Zhang et al, 2008). Finally, we have recently demonstrated that burn trauma induces thermogenically functional mitochondrial within the sWAT of mice (Porter et al, 2015), suggesting that burn injury is an ideal locale to study sWAT browning in humans.…”

Differential acute and chronic effects of burn trauma on murine skeletal muscle bioenergetics

“…We used a murine model of full-thickness burn trauma in the current study [15–18]. Similar to humans, hypermetabolism has been documented in similar murine models of burn trauma [19].…”