Treatment with a SOD mimetic reduces visceral adiposity, adipocyte death, and adipose tissue inflammation in high fat-fed mice

Authors

  • Karla M. Pires,

    1. Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
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  • Olesya Ilkun,

    1. Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
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  • Marina Valente,

    1. Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
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  • Sihem Boudina

    Corresponding author
    1. Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
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  • Funding agencies: This research was supported by a Scientist Development Grant 09SDG2220218 from the American Heart Association and a P30-HL-101310 from the National Institutes of Health (NIH) to Sihem Boudina. Karla M. Pires is supported by a post-doctoral training grant from “Assessoria de Cooperacao Internacional Coordenacao de Cooperacao Bilateral Programa CSF-Programa Ciência sem Fronteiras (COCBI)”. Olesya Ilkun is supported by T32DK091317 training grant from NIH/NIDDK. Marina Valente is supported by the Science without Border Undergraduate Fellowship from the Brazilian Scientific Mobility Programs.

  • Disclosure: The authors declared no conflict of interest.

  • Author Contributions: Karla M. Pires and Olesya Ilkun performed the experiments, researched data and carried out data analysis. Sihem Boudina designed the study, performed some experiments, research data, analyzed data and wrote the manuscript.

Abstract

Objective

Obesity is associated with enhanced reactive oxygen species (ROS) accumulation in adipose tissue. However, a causal role for ROS in adipose tissue expansion after high fat feeding is not established. The aim of this study is to investigate the effect of the cell permeable superoxide dismutase mimetic and peroxynitrite scavenger Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) on adipose tissue expansion and remodeling in response to high fat diet (HFD) in mice.

Design and Methods

Male C57BL/6j mice were fed normal chow or high fat diet (HFD) and treated with saline or MnTBAP for 5 weeks. The effects of MnTBAP on body weights, whole body energy expenditure, adipose tissue morphology, and gene expression were determined.

Results

MnTBAP attenuated weight gain and adiposity through a reduction in adipocyte hypertrophy, adipogenesis, and fatty acid uptake in epididymal (eWAT) but not in inguinal (iWAT) white adipose tissue. Furthermore, MnTBAP reduced adipocyte death and inflammation in eWAT and diminished circulating levels of free fatty acids and leptin. Despite these improvements, the development of systemic insulin resistance and diabetes after HFD was not prevented with MnTBAP treatment.

Conclusions

Taken together, these data suggest a causal role for ROS in the development of diet-induced visceral adiposity but not in the development of insulin resistance and type 2 diabetes.

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