Nutrient Overload Causes Rapid Accumulation of Myeloperoxidase in the Mesenteric Fat.

Abstract

Infiltration of adipose tissue by inflammatory cells is associated with adipocyte dysfunction and insulin resistance in obesity. Recent publications support an early role for neutrophils in this process. Neutrophils are the main source of the oxidant myeloperoxidase (MPO). Accordingly, we hypothesized a role for MPO in the adipocyte dysfunction induced by nutrient overload. C57BL/6 wild‐type mice were given either a control or a high‐fat meal (HFM, 60% fat, 20% carbohydrate, 20% protein) by gavage. Mesenteric and subcutaneous fat pads were isolated from mice at 1 and 3 hours post‐feeding to measure MPO content and activity by western blot analysis and colorimetric assay, respectively. Intravital microscopy of the mesenteric fat microcirculation was also used to monitor postprandial kinetics of leukocyte‐endothelium interactions (LEI). High‐fat meals increased MPO activity only in mesenteric fat pads with peak values observed at 1 h post‐feeding (p<0.001 versus control). Moreover, MPO activity remained elevated at 3 hours post‐feeding in the stromal vascular fraction of the visceral fat (p< 0.01 versus control). In the mesenteric fat microcirculation, LEI were elevated with peak rolling and adhesion occurring at 1 hour post‐feeding. Taken together these data demonstrate that nutrient overload causes a rapid activation of neutrophil trafficking and accumulation of MPO in the visceral fat.