Adipose browning response to burn trauma is impaired with aging
Abdikarim Abdullahi, Carly M. Knuth, Christopher Auger, Thibacg Sivayoganathan, Alexandra Parousis, Marc G. Jeschke
Abdikarim Abdullahi, Carly M. Knuth, Christopher Auger, Thibacg Sivayoganathan, Alexandra Parousis, Marc G. Jeschke
View: Text | PDF
Clinical Research and Public Health Aging Endocrinology

Adipose browning response to burn trauma is impaired with aging

Abstract

BACKGROUND The incidence of burn injuries in older patients is dramatically increasing as the population of older people grows. Despite the increased demand for elderly burn care, the mechanisms that mediate increased morbidity and mortality in older trauma patients are unknown. We recently showed that a burn injury invokes white adipose tissue browning that leads to a substantially increased hypermetabolic response associated with poor outcomes. Therefore, the aim of this study was to determine the effect of age on the metabolic adipose response of browning after a burn injury.METHOD One hundred and seventy patients with burn injury admitted to the Ross Tilley Burn Centre were prospectively enrolled and grouped by age as older (≥50 years) and young (≤35 years). Adipose tissue and sera were collected and analyzed for browning markers and metabolic state via histology, gene expression, and resting energy expenditure assays.RESULTS We found that older patients with burn injury lacked the adipose browning response, as they showed significant reductions in uncoupling protein 1 (UCP1) expression. This failure of the browning response was associated with reduced whole-body metabolism and decreased survival in older patients with burn injury. Mechanistically, we found that the adipose of both aged patients after burn trauma and aged mice after a burn showed impairments in macrophage infiltration and IL-6, key immunological regulators of the browning process after a severe trauma.CONCLUSION Targeting pathways that activate the browning response represents a potential therapeutic approach to improve outcomes after burn trauma for elderly patients.FUNDING NIH (R01-GM087285-01), Canadian Institutes of Health Research (grant no. 123336), and Canada Foundation for Innovation Leaders Opportunity Fund (no. 25407).

Authors

Abdikarim Abdullahi, Carly M. Knuth, Christopher Auger, Thibacg Sivayoganathan, Alexandra Parousis, Marc G. Jeschke

×

Figure 3

Increased mortality and impaired adipose remodeling in aged mice after a burn injury.

Options: View larger image (or click on image) Download as PowerPoint
Increased mortality and impaired adipose remodeling in aged mice after a...
(A) Kaplan-Meier survival curves of young vs. aged mice subjected to a 30% total body surface area burn injury. (B) Changes in inguinal WAT mass in young and aged mice 1 week after burn injury. (C) Plasma concentration of free fatty acids in young and aged mice 1 week after burn injury. (D) Immunohistochemistry H&E staining of subcutaneous WAT of young and aged mice. (E) Different lipid droplet size frequency in subcutaneous WAT isolated from young and aged mice. (F) Quantification of average lipid droplet size in subcutaneous WAT isolated from young and aged mice. (G) Quantification of the number of multilocular adipocytes in subcutaneous WAT isolated from young and aged mice. Data represent the mean ± SEM. *P < 0.05, vs. sham; #P < 0.05, vs. burn (n = 10). Scale bars: 100 μm. Statistical differences were determined using 2-way ANOVA followed by Bonferroni post hoc test.