Circulating Progenitor Cell Quantity and Colony‐Forming Capacity in Lean and Obese Adults

Abstract

Obesity is associated with chronic low‐grade inflammation and decreased tissue repair capacity. Circulating progenitor cells (CPCs) are a heterogeneous cell population involved in tissue repair, and include hematopoietic stem/progenitor cells (HSPCs) that are precursors to all mature hematopoietic cells. Rodent models have shown that acute inflammatory stimuli induce myeloid differentiation of HSPCs via Toll‐like receptor 4 (TLR4) signaling. However, the effects of a chronic inflammatory condition, like obesity, on CPC content and differentiation has not been previously examined in humans. The purpose of the present cross‐sectional study was to compare the quantity of various CPC populations, HSPCs expressing TLR4, and HSPC colony forming unit (CFU) capacity between obese (OB) and healthy weight (HW) adults. Participants were divided into HW (n=19) or OB (n=15) based on body mass index. Blood was collected for quantification of the following CPC populations: CPCs (CD34+), hematopoietic stem/progenitor cells (HSPCs: CD34+/CD45dim), HSPCs expressing TLR4 (TLR4+HSPCs: CD34+/CD45dim/TLR4+), bone marrow‐derived mesenchymal stromal cells (BM‐MSCs: CD45−/CD34+/CD31−/CD105+, adipose‐derived MSCs (AT‐MSCs;CD45−/CD34+,CD31−/CD105+), endothelial progenitor cells (EPCs: CD45−/CD34+/CD31+), endothelial cells (ECs; CD34+/CD31−), common myeloid progenitors (CMPs: Lineage−/CD34+/CD38+/CD123low/CD45RA−), and common lymphoid progenitors (CLP: Lineage−/CD34+/CD38+/CD10+) by flow cytometry. Granulocyte (CFU‐G), macrophage (CFU‐M), and mixed (CFU‐GM) colony forming capacity was also evaluated. HSPCs expressing TLR4 were lower (P<0.05) in the OB group compared to HW. Granulocyte, macrophage, and granulocyte‐macrophage colonies were greater (P<0.05) in the OB group compared to HW. Adipose tissue derived MSCs in the OB group trended to be lower (P=0.12) compared to HW. There were no differences between groups in the other cell populations analyzed. Here we show that HSPCs from OB have increased myeloid lineage CFU capacity. Enhanced myeloid CFU could have been due to increased differentiation of TLR4+HSPCs leading to an overall decrease in TLR4+HSPC quantity. Together, these data indicate that obesity is associated with increased myeloid differentiation of HSPCs, perhaps via differentiation of TLR4+HSPCs, which likely exacerbates the chronic inflammation observed in obesity.