4.7 Article Retracted Publication

被撤回的出版物: Myeloperoxidase Deletion Prevents High-Fat Diet-Induced Obesity and Insulin Resistance (Retracted article. See vol. 70, pg. 1912, 2021)

Journal

DIABETES
Volume 63, Issue 12, Pages 4172-4185

Publisher

AMER DIABETES ASSOC
DOI: 10.2337/db14-0026

Keywords

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Funding

  1. National Institutes of Health [HL-079584, HL-080499, HL-074399, HL-089920, HL-096032, HL-10488, AG047776, HL-105157]
  2. American Diabetes Association
  3. Warren Chair in Diabetes Research from the University of Oklahoma Health Sciences Center
  4. American Heart Association
  5. National Established Investigator Award of the American Heart Association

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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.

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