Oral Presentation Australian & New Zealand Obesity Society 2014 Annual Scientific Meeting

Human gastro-oesophageal adipose tissue (GO fat): A depot enriched in thermogenic beige/brige adipocytes (#68)

Frank L.S. Kyang 1 , Rebecca L. Stewart 2 , Brielle Wood 2 3 , Evgenii Borodachev 1 , Michael M. Swarbrick 2 4 , Reginald V. Lord 1 3
  1. St. Vincent's Institute for Applied Medical Research, Darlinghurst, NSW, Australia
  2. Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia
  3. University of Notre Dame Australia, Darlinghurst, NSW, Australia
  4. School of Medical Sciences, University of New South Wales, Kengington, NSW, Australia

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.