Myeloperoxidase deletion prevents high-fat diet-induced obesity and insulin resistance.

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 an HFD resulted in neutrophil infiltration and enhanced MPO expression and activity in epididymal white adipose tissue, 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. The 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 expression of proinflammatory cytokines. 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.

• Authors: Qilong Wang, Zhonglin Xie, Wencheng Zhang, Jun Zhou, Yue Wu, Miao Zhang, Huaiping Zhu, Ming-Hui Zou
• Journal: Diabetes (Diabetes) Vol. 63 Issue 12 Pg. 4172-85 (Dec 2014) ISSN: 1939-327X [Electronic] United States
• PMID: 25024373 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Retracted Publication)
• Copyright: © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Ion Channels
• Mitochondrial Proteins
• Ucp1 protein, mouse
• Uncoupling Protein 1
• Peroxidase

Topics

• Adipose Tissue (immunology)
• Adipose Tissue, Brown (immunology, metabolism)
• Animals
• Body Temperature Regulation (physiology)
• Cell Count
• Diet, High-Fat (adverse effects)
• Glucose Tolerance Test
• Inflammation (immunology)
• Insulin Resistance (genetics, immunology)
• Ion Channels (metabolism)
• Macrophages (cytology, immunology)
• Mice
• Mice, Knockout
• Mitochondria (metabolism)
• Mitochondrial Proteins (metabolism)
• Neutrophils (cytology, immunology)
• Obesity (enzymology, genetics, immunology)
• Oxygen Consumption
• Peroxidase (genetics, immunology, metabolism)
• Uncoupling Protein 1
• Up-Regulation