Metabolic endotoxemia directly increases the proliferation of adipocyte precursors at the onset of metabolic diseases through a CD14-dependent mechanism

Metabolic endotoxemia triggers inflammation, targets cells from the stroma-vascular fraction of adipose depots, and metabolic disease. To identify these cells we here infused mice with lipopolysaccharides and showed by FAGS analyses and BrdU staining that the number of small subcutaneous adipocytes, preadipocytes and macrophages increased in wild type but not in CD14-knockout (KO) mice. This mechanism was direct since in CD14K0 mice grafted subcutaneously and simultaneously with fat pads from CD14K0 and wild-type mice the concentration of cytokine mRNA was increased in the wild-type fat pad only. Conversely, the mRNA concentration of genes involved in glucose and lipid metabolism and the number of large adipocytes was reduced. Eventually, a pretreatment with LPS enhanced HFD-induced metabolic diseases. Altogether, these results show that metabolic endotoxemia increases the proliferation of preadipocytes through a CD14-dependent mechanism directly, without recruiting CD14-positive cells from non-adipose depot origin. This mechanism could precede the onset of metabolic diseases. (C) 2013 The Authors. Published by Elsevier GmbH. Open access under CC BY-NC-ND license