Background: Recently, thermogenic beige/brite adipocytes with potential anti-obesity effects have been isolated from rodent white adipose tissue. Beige/brite adipocytes are characterised by inducible uncoupling protein-1 (UCP1) expression, and by the cell surface markers TMEM26 and CD137 (Wu J et al. Cell 2012). In humans, beige/brite cells have been identified in several human adipose depots, including supraclavicular, mediastinal, retroperitoneal and intra-abdominal fat. These cells were proposed to express the marker CITED1 (Sharp LZ et al. PLoS One 2013). We aimed to identify beige/brite cells in human fat, to examine their relationship with obesity/diabetes and to establish an in vitro model.
Subjects and Methods: Adipose tissues (omental, gastro-oesophageal (GO fat) and abdominal subcutaneous) were obtained from 32 subjects undergoing routine abdominal surgery at SVH, Darlinghurst. This included 8 non-obese (3M/5F, BMI 21.7-27.1kg/m2), 11 obese (2M/9F, BMI 33.9-39.9 kg/m2) and 13 severely obese (6M/7F, BMI 41.3-57.2 kg/m2) subjects. Tissues were fixed for UCP1 immunohistochemistry, and mRNA expression of thermogenic genes (UCP1, PPARGC1A) and beige/brite identity (PRDM16, TMEM26, CD137, CITED1 and TBX15) was measured by RT-PCR.
Results: Half of all GO fat samples, and 44% of omental samples had detectable multilocular UCP1+ adipocytes. Beige/brite adipocyte prevalence was not associated with BMI or diabetes.
GO fat tended to express the highest levels of mRNAs encoding UCP1 (1.90-fold vs. omental fat, P=0.13) and PPARGC1A (1.99-fold vs omental fat, P=0.46); and in GO fat, the expression of these genes was significantly correlated (r=0.54, P=0.019). Of the three depots, GO fat had the highest expression of the beige/brite markers TMEM26 (2.40-fold vs. omental, P=0.035) and TBX15 (6.76-fold vs. omental, P<0.0001) and tended to have higher CD137 expression (11.9-fold vs. omental, P=0.15). TMEM26 expression in GO fat was highly correlated with UCP1 (r=0.63,P=0.0050). In contrast, CITED1 expression was not increased in GO fat (0.84-fold vs. omental, P=0.40).
Conclusion: GO fat contains an abundance of thermogenic beige/brite adipocytes, and is therefore a potential source of these cells for in vitro studies.