Key result
Mediastinal adipose tissue shows brown fat characteristics with 24-fold higher UCP1 expression versus subcutaneous fat.
Why the study?
The mediastinal adipose tissue depot in adult humans may contain brown adipose tissue, but its characteristics compared to subcutaneous adipose tissue are not well understood.
Cross-Sectional (n=33)
No
Human mediastinal adipose tissue exhibits molecular and microscopic characteristics of brown adipose tissue, which may have implications for understanding its role in cardiometabolic risk.
Mediastinal fat may harbor BAT-like properties distinct from subcutaneous depots; leaves open any cardiometabolic role pending prospective data.
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 μm(2), P<0.001). CONCLUSIONS: Human mediastinal adipose tissue displays some characteristics of BAT when compared with the subcutaneous depot at microscopic and molecular levels.
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Cheung et al. (2013) conducted a cross-sectional in Patients undergoing elective open-heart aortic valve surgery (n=33). Mediastinal adipose tissue vs. Subcutaneous adipose tissue was evaluated on UCP1 gene expression (24-fold, p=<0.001). Human mediastinal adipose tissue displayed characteristics of brown fat, including a 24-fold higher expression of UCP1 and significantly smaller adipocytes compared to subcutaneous adipose tissue.
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