Abstract 15440: Dynamics of Adipocyte and Endothelial Progenitor Cell Pools in Expanding Adipose Tissue

Abstract

Objective: Obesity is a major risk factor for the development of several chronic diseases including type 2 diabetes and cardiovascular disease. Proper fat storage in white adipose tissue (WAT) is required to maintain insulin sensitivity and to preserve (cardio)vascular health. We hypothesize that endothelial and adipocyte progenitor cell populations (EPCs and APCs, respectively) must be appropriately balanced for physiological, as opposed to pathological, remodeling of WAT. Methods and Results: To determine the impact of nutrient excess on stem/progenitor cells in epididymal WAT, male C57BL/6J mice were placed on a high fat diet (HFD; 60% fat) for 12 weeks and changes in WAT stem cell populations were measured in the stromal vascular fraction by flow cytometry. Although the APC (CD24+/CD29+/Sca+/CD14-/CD45-) population, which has the capacity to differentiate into adipocytes both in vitro and in vivo , was not significantly changed with diet, Flk+/Sca+ EPCs were diminished, promoting a 4-fold decrease in the EPC/APC ratio (p <0.05, n = 6/group). To determine whether this deficit may be due to poor stem cell recruitment, mice were irradiated, and the bone marrow was repopulated with GFP+ donor marrow. The transplanted mice were then placed on a low fat diet (LFD; 10% fat) or HFD for 12 weeks, and WAT progenitor cells were again measured. Greater than 95% of the putative APCs in the WAT of HF-fed mice were GFP+ (p<0.0001, n=7-8/group), indicating a bone marrow-derived origin. Unexpectedly, less than 1% of the EPCs were GFP+ (p<0.001, n=7-8/group), which suggests that EPCs present in WAT are not derived from bone marrow in adult mice. Confocal analysis of WAT from HF-fed, bone marrow-transplanted mice showed little evidence of significant APC differentiation into triglyceride-laden adipocytes, suggesting that conditions associated with nutrient excess may impair the ability of the adipose organ to store fat properly. Conclusions: These results demonstrate that putative APCs, and not EPCs, in epididymal WAT are derived from bone marrow. Furthermore, our data suggest that conditions of nutrient excess promote an imbalance in EPCs and APCs, the stoichiometry of which may be critical for the development of new adipocytes and for proper storage of fat.