High-fat diet selectively decreases bone marrow lin- /CD117+ cell population in aging mice through increased ROS production

Abstract

Bone marrow (BM) stem cells (BMSCs) are an important source for cell therapy. The outcome of cell therapy could be ultimately associated with the number and function of donor BMSCs. The present study was to evaluate the effect of long-term high-fat diet (HFD) on the population of BMSCs and the role of reactive oxygen species (ROS) in aging mice. Forty-week-old male C57BL/6 mice were fed with HFD for 3 months with regular diet as control. Experiments were repeated when ROS production was reduced in mice treated with N-acetylcysteine (NAC) or using mice overexpressing antioxidant enzyme network (AON) of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase. BM and blood cells were analyzed with flowcytometry for lineage negative (lin^- ) and Sca-1⁺ , or lin^- /CD117⁺ , or lin^- /CD133⁺ cells. Lin^- /CD117⁺ cell population was significantly decreased with increased intracellular ROS and apoptosis and decreased proliferation in BM, not in blood, in HFD-treated mice without change for Sca-1⁺ or CD133⁺ cell populations in BM or blood. NAC treatment or AON overexpression effectively prevented HFD-induced intracellular ROS production and reduction of BM lin^- /CD117⁺ population. These data suggested that long-term HFD selectively decreased BM lin^- /CD117⁺ cell population in aging mice through increased ROS production.

Keywords: N-;acetylcysteine; bone marrow stem cells; high-fat diet; oxidative stress; reactive oxygen species.