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Monoamine oxidase is a source of cardiac oxidative stress in obese rats: the beneficial role of metformin

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Abstract

Diet-induced metabolic diseases, such as obesity, metabolic syndrome, and type 2 diabetes (T2DM) are the global threatening epidemics that share cardiovascular oxidative stress as common denominator. Monoamine oxidase (MAO) has recently emerged as a constant source of reactive oxygen species (ROS) in DM. Metformin, the first-line drug in T2DM, elicits cardiovascular protection via pleiotropic effects. The present study was aimed to assess the contribution of MAO to the early cardiac oxidative stress in a rat model of high-calorie junk food (HCJF) diet-induced obesity and prediabetes and whether metformin can alleviate it. After 6 months of HCJF, rats developed obesity and hyperglycemia. Hearts were isolated and used for the evaluation of MAO expression and ROS production. Experiments were performed in the presence vs absence of metformin (10 µM) and MAO-A and B inhibitors (clorgyline and selegiline, 10 µM), respectively. Both MAO isoforms were overexpressed and led to increased ROS generation in cardiac samples harvested from the obese animals. Acute treatment with metformin and MAO inhibitors was able to mitigate oxidative stress. More important, metformin downregulated MAO expression in the diseased samples. In conclusion, MAO contributes to oxidative stress in experimental obesity and can be targeted with metformin.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This research was funded by the university internal grant code 6POSTDOC/1871/12.02.2020 (A.S.).

Funding

Funding was provided by “Victor Babes” University of Medicine and Pharmacy, Timişoara, Romania (6POSTDOC/1871/12.02.2020).

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Author notes

  1. Adrian P. Merce and Loredana N. Ionică have contributed equally to this work.

Authors and Affiliations

  1. Department of Functional Sciences - Pathophysiology, “Victor Babeş” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041, Timişoara, Romania

    Adrian P. Merce, Loredana N. Ionică, Anca M. Bînă, Claudia Borza, Adrian Sturza & Danina M. Muntean

  2. Center for Translational Research and Systems Medicine, “Victor Babeş” University of Medicine and Pharmacy, EftimieMurgu Sq. No. 2, 300041, Timişoara, Romania

    Adrian P. Merce, Loredana N. Ionică, Anca M. Bînă, Claudia Borza, Adrian Sturza & Danina M. Muntean

  3. Department of Internal Medicine VII - Diabetes, Nutrition, Metabolic Diseases, “Victor Babeş” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041, Timişoara, Romania

    Simona Popescu

  4. Department of Infectious Diseases-Parasitology, ”Victor Babeş” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041, Timişoara, Romania

    Rodica Lighezan

  5. Department of Cardiology - Cardiology II, “Victor Babeş” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041, Timişoara, Romania

    Lucian Petrescu

  6. Department of Surgery - Surgical Semiotics, “Victor Babeş” University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041, Timişoara, Romania

    Octavian M. Creţu

  7. Center for Hepato‑Biliary and Pancreatic Surgery, “Victor Babeş” University of Medicine and Pharmacy Timişoara, Eftimie Murgu Sq. No. 2, 300041, Timişoara, Romania

    Octavian M. Creţu

  8. Department of Functional Sciences III – Pathophysiology, Center for Translational Research and Systems Medicine, “Victor Babeş” University of Medicine and Pharmacy of Timişoara , Eftimie Murgu Sq. No. 2, 300041, Timişoara, Romania

    Adrian Sturza & Danina M. Muntean

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  1. Adrian P. Merce
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Contributions

APM: investigation, formal analysis LNI: investigation, original draft preparation, formal analysis; AMB: methodology, investigation; SP: visualization, supervision; RL: investigation visualization; LP: supervision; CB: visualization, supervision; A.S.: data curation, writing—review and editing; DMM: conceptualization, writing—review and editing; OMC: project administration, funding acquisition. All authors have read and agreed to the published version of the manuscript.

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Merce, A.P., Ionică, L.N., Bînă, A.M. et al. Monoamine oxidase is a source of cardiac oxidative stress in obese rats: the beneficial role of metformin. Mol Cell Biochem 478, 59–67 (2023). https://doi.org/10.1007/s11010-022-04490-5

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