409 Evidence of Functional Brown Adipose Tissue in Children With Severe Burns

Abstract

Introduction

Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis in mammals owing to the expression of uncoupling protein-1 (UCP-1), which uncouples mitochondrial respiration from ATP production. It has recently been observed that adult humans have functional BAT. While it has been theorized that uncoupled mitochondrial respiration contributes to the hypermetabolic response to burns, whether patients with severe burns have functional BAT remains unknown.

Methods

We collected sub-platysmal adipose tissue (sPAT) (n=5 samples) from patients undergoing reconstructive surgeries and peri-renal adipose tissue (pRAT) (n=2 samples) from patients at autopsy. Sub-cutaneous white adipose tissue (scWAT) samples were also collected. High-resolution respirometry was performed on permeabilized tissue samples to determine respiration. Titration of the UCP-1 inhibitor guanosine diphosphate (GDP) was used to determine the presence or absence of BAT in sPAT and scWAT. Histology was also performed on pRAT and scWAT samples.

Results

The average of patients providing sPAT was 9 ± 1 years. sPAT adipose tissue had a respiratory capacity 26-fold higher than scWAT (68.5 ± 39.7 vs. 2.6 ± 1.5 pmol/s/mg, p<0.001). GDP titration reduced respiration in sPAT (-38.9 ± 17.7 pmol/s/mg) but not scWAT mitochondria (-0.08 ± 0.07 pmol/s/mg), providing direct evidence of functional BAT within sPAT. Histological analysis showed that pRAT had distinct areas with an abundance of small multi-locular cells (adipocytes containing numerous small lipid droplets), whereas scWAT exhibited larger mainly uni-locular cells (adipocytes containing one large lipid droplet).

Conclusions

We provide novel functional and histological evidence of BAT in patients with severe burns. The functional signature of UCP-1 in sPAT of burned patients indicates that this BAT is thermogenic, and therefore may contribute to the hypermetabolic response to burn injury.

Applicability of Research to Practice

We have identified BAT in burned patients as a component of the metabolic response to burn injury. The regulatory and homeostatic qualities of this tissue render it a potential target to modulate the hypermetabolic response to burn injury.