Abstract
Background:The amount of intra-thoracic fat, of which mediastinal adipose tissue comprises the major depot, is related to various cardiometabolic risk factors. Autopsy and imaging studies indicate that the mediastinal depot in adult humans could contain brown adipose tissue (BAT). To gain a better understanding of this intra-thoracic fat depot, we examined possible BAT characteristics of human mediastinal in comparison with subcutaneous adipose tissue.Materials and methods:Adipose tissue biopsies from thoracic subcutaneous and mediastinal depots were obtained during open-heart surgery from 33 subjects (26 male, 63.7±13.8 years, body mass index 29.3±5.1 kg m−2). Microarray analysis was performed on 10 patients and genes of interest confirmed by quantitative PCR (qPCR) in samples from another group of 23 patients. Adipocyte size was determined and uncoupling protein 1 (UCP1) protein expression investigated with immunohistochemistry.Results:The microarray data showed that a number of BAT-specific genes had significantly higher expression in the mediastinal depot than in the subcutaneous depot. Higher expression of UCP1 (24-fold, P<0.001) and PPARGC1A (1.7-fold, P=0.0047), and lower expression of SHOX2 (0.12-fold, P<0.001) and HOXC8 (0.14-fold, P<0.001) in the mediastinal depot was confirmed by qPCR. Gene set enrichment analysis identified two gene sets related to mitochondria, which were significantly more highly expressed in the mediastinal than in the subcutaneous depot (P<0.01). No significant changes in UCP1 gene expression were observed in the subcutaneous or mediastinal depots following lowering of body temperature during surgery. UCP1 messenger RNA levels in the mediastinal depot were lower than those in murine BAT and white adipose tissue. In some mediastinal adipose tissue biopsies, a small number of multilocular adipocytes that stained positively for UCP1 were observed. Adipocytes were significantly smaller in the mediastinal than the subcutaneous depot (cross-sectional area 2400±810 versus 3260±980 μm2, P<0.001).Conclusions:Human mediastinal adipose tissue displays some characteristics of BAT when compared with the subcutaneous depot at microscopic and molecular levels.
Highlights
Mediastinal adipose tissue is situated within the mediastinum, inside the thorax, but outside the pericardium that encloses the heart and accounts for B70% of total intra-thoracic fat.[1,2,3] The nomenclature of this depot is somewhat confusing as it has been variously described as intra-thoracic[1,4] extra-pericardial mediastinal[2] and pericardial[3,5] adipose tissue, but all of these encompass the mediastinal depot studied here
We first compared in the two depots the expression of selected genes that had previously been described as brown adipose tissue (BAT) and white adipose tissue (WAT) markers in humans and/or mice, including transcription factors involved in adipocyte differentiation[9,12,17,22,23,24,25,26,27,28,29,30,31,32,33] (Table 2)
We considered genes suggested to discriminate between BAT and WAT in cell/animal models
Summary
Mediastinal adipose tissue is situated within the mediastinum, inside the thorax, but outside the pericardium that encloses the heart and accounts for B70% of total intra-thoracic fat.[1,2,3] The nomenclature of this depot is somewhat confusing as it has been variously described as intra-thoracic[1,4] extra-pericardial mediastinal[2] and pericardial[3,5] adipose tissue, but all of these encompass the mediastinal depot studied here. The amount of intra-thoracic fat, of which mediastinal adipose tissue comprises the major depot, is related to various cardiometabolic risk factors. To gain a better understanding of this intra-thoracic fat depot, we examined possible BAT characteristics of human mediastinal in comparison with subcutaneous adipose tissue. RESULTS: The microarray data showed that a number of BAT-specific genes had significantly higher expression in the mediastinal depot than in the subcutaneous depot. No significant changes in UCP1 gene expression were observed in the subcutaneous or mediastinal depots following lowering of body temperature during surgery. UCP1 messenger RNA levels in the mediastinal depot were lower than those in murine BAT and white adipose tissue. CONCLUSIONS: Human mediastinal adipose tissue displays some characteristics of BAT when compared with the subcutaneous depot at microscopic and molecular levels
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
