Poster Presentation The Annual Scientific Meeting of the Australian Diabetes Society and the Australian Diabetes Educators Association 2013

Browning of human subcutaneous adipose tissue progenitor cells in lean and obese adults. (#281)

Andrew L Carey 1 , Camilla Vorlander 1 , Medini Reddy-Luthmoodoo 1 , Alaina K Natoli 1 , Melissa F Formosa 1 , David Bertovic 1 , Mitchell J Anderson 1 , Stephen J Duffy 1 , Bronwyn A Kingwell 1
  1. Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia

Increasing brown adipose tissue (BAT) is a promising potential therapeutic for obesity and associated disorders. In addition to the recent conclusive identification of functional BAT in adult humans, rodent studies indicate resistance to obesity is associated with presence of brown (or beige/brite) adipocytes in traditional white adipose tissue (WAT) rather than BAT depots. Further, certain fat pads retain greater capacity than others for ‘browning’, the process whereby certain cells in WAT pads gain BAT cell properties.

Human supraclavicular BAT is known to contain cells that express the BAT-specific protein uncoupling protein-1 (UCP1) either via direct analysis of ex-vivo biopsy tissue, or in vitro when precursor cells are grown in culture. Low levels of UCP1 mRNA have also been detected in human white fat biopsies. The purpose of this study was therefore to determine whether precursor cells extracted from human adult subcutaneous WAT can differentiate into adipocytes in-vitro that express key markers of BAT/browning, and whether this differs between lean and obese young adult males.

When grown in BAT differentiation media, cell lines from both lean and obese groups differentiated into adipocytes, as indicated by oil red-O staining, the lipolytic response to stimulation with dibutyral cyclic-AMP, and expression of adipogeneic genes (FABP4, PPARG). These responses were not different between groups. Both cell lines also equally increased expression of the thermogenic-responsive gene PPARGC1A (PGC-1α). As expected for a mixed cell population, cultures highly and equally expressed both white (HOXC9) and beige-specific (CITED1) genes, as well as UCP1. Interestingly, UCP1 protein content was significantly greater after differentiation in cultures from lean compared with obese individuals (p<0.05).

In conclusion, classical WAT depots (ie, human subcutaneous abdominal fat) can attain BAT characteristics, but this may be reduced in obesity. Future therapeutic strategies should therefore target both BAT and WAT, and further human studies are required to determine the browning capacity of various WAT depots.