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Deficiency of glutathione peroxidase-1 and catalase attenuated diet-induced obesity and associated metabolic disorders

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Abstract

Aims

Oxidative stress has been considered to contribute to the development of obesity-related metabolic disorders including insulin resistance. To the contrary, deficiency of an anti-oxidizing enzyme, glutathione peroxidase (GPx)-1, was reported to enhance insulin signaling, suggesting that oxidative stress may inhibit the development of type 2 diabetes. However, the beneficial effects of the absence of GPx-1 in metabolic homeostasis, including body weight control, have not yet been clearly manifested. To clarify the relationship between oxidative stress and obesity-related metabolic disorders, we investigated another mouse deficient with both GPx-1 and catalase (Cat).

Methods

C57BL/6J wild-type and GPx-1−/− × Cat−/− mice were fed with a high-fat diet (60% fat) or a normal chow diet for 16 weeks and were investigated for metabolic and histological studies.

Results

Body weight gain was significantly reduced, and glucose metabolism as well as hepatic steatosis was obviously improved in the GPx-1−/− × Cat−/− mice. The serum levels of insulin and total cholesterol were also significantly lowered. For the underlying mechanism, inflammation was attenuated and expression of markers for fat browning was enhanced in the visceral white adipose tissues.

Conclusions

Oxidative stress due to deficiency of GPx-1 and Cat may improve obesity-related metabolic disorders through attenuation of inflammation and fat browning.

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Funding

This study was supported by a grant from Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C0050).

Author information

Author notes

  1. Hyung-Ran Kim and Eun-Jeong Choi: Equal contribution to the first authorship.

Authors and Affiliations

  1. Department of Microbiology, Ewha Womans University Graduate School of Medicine, Magokdongro 2-25, Gangseo-Gu, Seoul, 07804, Republic of Korea

    Hyung-Ran Kim, Eun-Jeong Choi & Ju-Young Seoh

  2. Department of Pathology, National Health Insurance Cooperation Ilsan Hospital, Koyang, Republic of Korea

    Jeong-Hae Kie

  3. Department of Surgery, Ewha Womans University Graduate School of Medicine, Gangseo-Gu, Seoul, Republic of Korea

    Joo-Ho Lee

  4. Mediplant Research Institute of Bioscience, Mapo-Gu, Seoul, Republic of Korea

    Joo-Ho Lee & Ju-Young Seoh

Authors
  1. Hyung-Ran Kim
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  2. Eun-Jeong Choi
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  3. Jeong-Hae Kie
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  4. Joo-Ho Lee
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Corresponding authors

Correspondence to Joo-Ho Lee or Ju-Young Seoh.

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The authors declare no conflicts of interest.

Ethical standard statement

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Institutional Animal Care and Use Committee of Ewha Womans University Graduate School of Medicine, Permit Number: 10-0133).

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Kim, HR., Choi, EJ., Kie, JH. et al. Deficiency of glutathione peroxidase-1 and catalase attenuated diet-induced obesity and associated metabolic disorders. Acta Diabetol 57, 151–161 (2020). https://doi.org/10.1007/s00592-019-01388-5

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  • DOI: https://doi.org/10.1007/s00592-019-01388-5

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