Transplantation of Pre‐adipocytes and Stem Progenitors from Brown Adipose Tissue (BAT) Stromal Vascular Fraction (SVF) Improves Glucose Metabolism of the Recipients

Abstract

Brown adipose tissue (BAT) is a thermogenic tissue that can dissipate chemical energy in the form of heat and has recently emerged as a potential therapeutic target against obesity and type 2 diabetes. Previous work in our laboratory has shown that increasing the amount of BAT by transplantation greatly improves glucose homeostasis and insulin sensitivity in a mouse model. We hypothesize that specific cell types within the BAT are responsible for this effect. The cell types in BAT include mature brown adipocytes and the stromal vascular fraction (SVF), which contains various cell types including pre‐adipocytes, stem progenitor cells and immune cells. Importantly, while tissue transplantation is a viable option in rodent models, it is not easily adaptable to human application. Transplantation of cells however is a more translatable approach for human use. Here, we isolated the SVF and cultured pre‐adipocytes and stem‐progenitor cells from BAT to identify if these cell types can improve glucose homeostasis upon transplantation. Cells were isolated from Luciferase Transgenic and then differentiated by adipogenic induction and injected into the visceral cavity of recipient wild‐type C57BL/6 mice on days 0, 1, 3, 6 and 8 of differentiation. We injected low (100k) and high (1.2 million) cell numbers. Metabolic tests (including measurements of glucose tolerance and insulin sensitivity) were performed at 4 weeks post‐transplantation. We found that transplantation of pre‐adipocytes on days 3, 6 and 8 of differentiation improve glucose tolerance in recipient mice (40.5% improvement [day 3], 10.34% improvement [day 6] and 26.32% improvement [day 8] in glucose tolerance test area under the curve (AUC) at 4 weeks post‐transplantation). These exciting data indicate that that pre‐adipocytes and stem progenitor cells isolated from BAT SVF and differentiated into adipocytes can improve glucose metabolism upon transplantation. These data will be used to develop efficient identification and transplantation approaches for cell types from BAT SVF that improve glucose homeostasis and be an important strategy to combat obesity and type 2 diabetes.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.