Oral Presentation ANZOS-Breakthrough Discoveries Joint Annual Scientific Meeting 2018

Identification and characterisation of metabolically distinct human adipocyte precursor cells (#75)

Arthe Raajendiran 1 2 , Geraldine Ooi 3 4 , Ashlee Clark 2 , Jacqueline Bayliss 1 2 , Paul O'Brien 4 , Renea Taylor 2 , Matthew Rodeheffer 5 , Paul Burton 3 4 , Matthew Watt 1 2
  1. Physiology, The University of Melbourne, Parkville, VIC, Australia
  2. Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  3. Upper Gastro-Intestinal Surgery, The Alfred, Melbourne, VIC, Australia
  4. Centre for Obesity Research & Education, Monash University, Melbourne, VIC, Australia
  5. Department of Molecular Cell and Developmental Biology, Yale University, New Haven, CT, USA

An enlarged adipose tissue (AT) mass, as seen in obesity, is related to the onset of insulin resistance that further perpetuates a constellation of life-threatening metabolic diseases such as type 2 diabetes, cardiovascular diseases and some forms of cancer. While understanding the expansion of a regional adipose tissue mass helps to delineate the specific cellular processes promoting health and disease, the adipocytes regulating the mass of an AT depot are differentiated from the tissue-resident adipocyte precursor cells (APCs) whose identity in humans remain largely unknown. Hence, we aimed to identify the human APCs located within the regional AT depots obtained from visceral, abdominal subcutaneous and gluteal-femoral regions to assess their adipogenic potential, metabolic properties and any correlations with metabolic disease. 

We have discovered that human AT consists of three transcriptionally (RNASeq) distinct APCs in the lineage depleted (CD31-CD45-) stromal vascular fraction (SVF) using fluorescent activated cell sorting technology and termed them as CD34-, CD34lo and CD34hi APCs. All three precursor cells differentiated into mature adipocytes in vitro. Freshly sorted human CD34hi APCs formed mature adipocytes when xenotransplanted into immunodeficient mice and the assessment of in vivo adipogenesis of CD34- and CD34lo APCs is still ongoing.

Rates of lipolysis, fatty acid uptake were higher in CD34hi compared with CD34- and CD34lo APC-derived adipocytes in vitro, the latter having very low fatty acid turnover. Interestingly, only the CD34- adipocytes displayed enhanced thermogenic potential in vitro. Importantly, the proportion of CD34hi APCs was higher and CD34- APCs was lower in the AT 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 metabolic capacities and distribution in metabolically healthy and non-healthy adipose tissue depots.

 

Funding: NHMRC, Australia.