Morphological Changes in Subcutaneous White Adipose Tissue After Severe Burn Injury

Abstract

Introduction Severe burn injury produces a plethora of metabolic abnormalities which contribute to the prolonged morbidity of burn survivors. We have recently demonstrated trans-differentiation of white adipose tissue following burn trauma, towards a more thermogenic phenotype. However, the impact of burn injury on subcutaneous WAT (sWAT) morphology in humans is unknown. Here, we studied the effect of severe burn injury on the architecture of sWAT. Methods sWAT was collected from eleven severely burned children (11±3 yrs; 55±16% total body surface area burned) and twelve non-burned healthy children (9±3 yrs). Histology, electron microscopy, immunohistochemistry and immunofluorescence were performed on fixed adipose tissue sections. sWAT cytokine and collagen concentrations were measured by multiplex assay and sirus/fast green staining method respectively. Results sWAT histology demonstrated multiple fat droplets, significantly (p<0.05) reduced mean cell size (104±6µm vs. 68±3µm) and higher collagen content (7±0.8 vs 4±0.4). sWAT from burn victims stained positive for CD68 suggesting infiltration of macrophages. Further, electron microscopic analysis showed multiple fat droplets and greater mitochondrial abundance in sWAT of burn survivors. In agreement with this, mitochondrial respiratory capacity in the leak and coupled state increased by 100% in sWAT of burned children from 1 to 3 week post injury. The cytokines IL-6, IL-8, IL-13, IL-1a, IL-1b), MCP-1 and TNF-α were all significantly greater in the sWAT of burned children vs. healthy children (P<0.05). Furthermore, IL-6, IL-8, IL1-a, IL-1b and TNF-α significantly increased after injury in sWAT of burned children (P<0.05). Conclusions This study provides the detailed evidence of morphological and functional changes in sWAT of burn survivors which was associated with tissue inflammation. Applicability of Research to Practice A better understanding of morphological and functional changes in sWAT will help discern the mechanisms underlying hypermetabolism in burned patients.

Adipose tissue: between the extremes

“…Cardiac fibrosis is also noted. Of note, patients with burn injury also display a higher collagen content in their adipose tissue, arguing for a role of adipose tissue remodeling in burn injuries, too (Saraf et al, 2016 There certainly is evidence for increased fibrosis in cachectic adipose tissue, both in mice and men (Mracek et al, 2011;Batista et al, 2016;Luo et al, 2016).…”

“…However, whether this is cause or consequence of the tissue wasting in cachexia remains to be investigated. Of note, patients with burn injury also display a higher collagen content in their adipose tissue, arguing for a role of adipose tissue remodeling in burn injuries, too (Saraf et al, 2016).…”

Macrophages Switch: The Fate of Adipose Tissue in Obesity

“…Moreover tissue cytokines IL-6, IL-8, IL-13, IL-1α, IL-1β, MCP-1, and TNF-α were all significantly greater in the sWAT of burned vs healthy subjects, providing an ostensible link between morphological/functional changes in sWAT and tissue inflammation [19]. Arachidonic acid is elevated in sWAT, and correlate strongly with macrophage presence in obese women with type 2 diabetes mellitus [20].…”

White adipose tissue browning in critical illness: A review of the evidence, mechanisms and future perspectives

“…The authors suggested these changes as potential contributors of disorders such as lipolysis, fibrosis and hypermetabolism in burn, mediated by inflammation. 16 It should be noted that subcutaneous WAT samples were obtained from different anatomical regions in this study. In addition, WAT interleukin (IL)-13 levels were higher in the children with burns compared with the healthy group.…”