Identifying the role of depot specific adipocyte precursors in the development of obesity and type 2 diabetes

A Raajendiran1, P Burton2, P O'Brien3, RA Taylor1 and MJ Watt1

  1. Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, VIC
  2. Department of Upper Gastro Intestinal Surgery, The Alfred hospital, Prahran, VIC
  3. Centre for Obesity Research and Education, Monash University, Clayton, VIC

Obesity induced by adipose tissue expansion is associated with metabolic diseases, including type 2 diabetes. However, not all adipose tissue is the same. Expansion of visceral (VAT) and abdominal subcutaneous (ASAT) adipose tissues is associated with metabolic disease and, in contrast, expansion of gluteal and femoral (GFAT) adipose tissue most likely protects against metabolic disease. Whether the intrinsic, cell-autonomous properties of adipocytes located within these regions confer these metabolic differences is unknown. Hence, we aimed to identify the adipocyte progenitor cells (APCs) present in these adipose tissue depots and assess their metabolic properties. We identified APCs through Fluorescent Activated Cell Sorting as CD31CD45CD29+CD34hi, CD31CD45CD29+CD34lo and CD31CD45CD29+CD34 from the stromal vascular fraction (SVF) of human (N=16) VAT, ASAT and GFAT and isolated them. The number of SVF cells was higher in GFAT (P=0.0004) than in VAT and ASAT. The proportion of CD34+ APCs was similar in all the depots. More interestingly, the number and proportion of CD34hi APCs was high in VAT (P=0.0254). In contrast, CD34lo and CD34 APCs were high in GFAT (P= 0.0014 & 0.0004). We then subjected the sorted cells to RNASeq analysis, in vitro adipogenic potential and metabolic assays. The transcriptomic profile of CD34hi, lo & – cells were distinct from each other. The APCs from all depots had similar adipogenic gene expression with lipid loading capacity being high in ASAT CD34lo & hi compared with other APCs. Initial metabolic studies indicate that CD34hi cells from subcutaneous tissues have increased capacity for fatty acid storage and reduced capacity for lipogenesis. In conclusion, we have identified bona fide APC populations in human adipose tissues. The results demonstrate that these APCs are more highly populated in GFAT compared with VAT and ASAT and they appear to have intrinsic metabolic differences, which in turn might drive the fate of adipose tissue.