Oral Presentation ANZOS-OSSANZ-AOCO Joint Annual Scientific Meeting 2017

Identification and characterisation of human adipocyte precursor cells (#49)

Arthe Raajendiran 1 , Geraldine Ooi 2 , Paul R Burton 2 , Paul O'Brien 3 , Renea A Taylor 1 , Matthew S Rodeheffer 4 , Matthew J Watt 1
  1. Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program; The Department of Physiology, Faculty of Biomedical and Psychological Sciences, Monash University, Clayton, VIC, Australia
  2. The Alfred, Melbourne, VIC, Australia
  3. Centre for Obesity Research & Education, Monash University, Melbourne, VIC, Australia
  4. Department of Molecular Cell and Developmental Biology, Yale University, New Haven, CT, USA

The formation of new mature adipocytes is strictly dependent on the presence of tissue resident adipocyte precursor cells (APCs) and the identity of human APCs remain largely unknown. Moreover, lipid metabolism in mature adipocytes is influenced by their anatomical location. Expanding visceral (VAT) and abdominal subcutaneous (ASAT) adipose tissues are often associated with metabolic diseases and contrastingly, expanding gluteo-femoral (GFAT) adipose tissue protects against metabolic diseases. Whether the site-specific properties of adipocytes located within these regions confer these metabolic differences is unknown. Hence, we aimed to identify the APCs present in these adipose tissue depots and assess their metabolic properties. 

We identified and isolated three APCs through Fluorescent Activated Cell Sorting as CD31-CD45-CD29+CD34hi, CD31-CD45-CD29+CD34lo and CD31-CD45-CD29+CD34- from the stromal vascular fraction (SVF) of human (N=20) VAT, ASAT and GFAT. The APCs made up 30-40% of all SVF cells and GFAT was enriched with more APCs when compared with ASAT and VAT. The subcutaneous depots were highly enriched with CD34- APCs compared with CD34lo and CD34hi APCs. VAT was enriched with similar numbers of CD34- and CD34hi. RNAseq analysis identified marked differences in the transcriptome of the three APCs and there were subtle differences in their proliferative capacities. All three APCs were able to undergo adipogenesis and form mature adipocytes in vitro. 

The differentiated APCs exhibited differences in their metabolic capacities. Rates of lipolysis and fatty acid uptake and storage were higher in CD34hi compared with CD34- and CD34lo APCs, the latter having very low fatty acid turnover. Interestingly, the proportion of CD34hi APCs was higher in the VAT of individuals with type 2 diabetes, suggesting that dysregulated lipolysis commonly observed in these individuals may be attributed to alterations in APC abundance. Summarily, we have identified three distinct bona fide APCs varying in their depot-specific abundance and metabolic capacities.