Myeloperoxidase Deletion Prevents High-Fat Diet-induced Obesity and Insulin Resistance

  1. Ming-Hui Zou*
  1. Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
  1. *Corresponding Author: Ming-Hui Zou, E-mail: ming-hui-zou{at}ouhsc.edu

Abstract

Activation of myeloperoxidase (MPO), a heme protein primarily expressed in granules of neutrophils, is associated with the development of obesity. However, whether MPO mediates high fat diet (HFD)-induced obesity and obesity-associated insulin resistance remains to be determined. Here, we found that consumption of a HFD resulted in neutrophil infiltration and enhanced MPO expression and activity in epididymal white adipose tissue (WAT), with an increase in body weight gain and impaired insulin signaling. MPO knockout (MPO-/-) mice were protected from HFD-enhanced body weight gain and insulin resistance. MPO inhibitor 4-aminobenzoic acid hydrazide reduced peroxidase activity of neutrophils and prevented HFD-enhanced insulin resistance. MPO deficiency caused high body temperature via upregulation of uncoupling protein-1 and mitochondrial oxygen consumption in brown adipose tissue. Lack of MPO also attenuated HFD-induced macrophage infiltration and proinflammatory cytokines expression. We conclude that activation of MPO in adipose tissue contributes to the development of obesity and obesity-associated insulin resistance. Inhibition of MPO may be a potential strategy for prevention and treatment of obesity and insulin resistance.

  • Received January 7, 2014.
  • Accepted July 8, 2014.

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