title: 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.affiliation: Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Qilong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Huaiping
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Section of Molecular Medicine, Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK ming-hui-zou@ouhsc.edu.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Zou
mesh_terms: D000273:Adipose Tissue / Q000276:immunology; D002001:Adipose Tissue, Brown / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology; D002452:Cell Count; D059305:Diet, High-Fat / Q000009:adverse effects*; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000276:immunology; D007333:Insulin Resistance / Q000235:genetics* / Q000276:immunology; D007473:Ion Channels / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D009765:Obesity / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D010101:Oxygen Consumption; D009195:Peroxidase / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000071256:Uncoupling Protein 1; D015854:Up-Regulation
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D009195:Peroxidase