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Acetate supplementation restores testicular function by modulating Nrf2/PPAR-γ in high fat diet-induced obesity in Wistar rats

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Abstract

Purpose

Several studies have established impaired testicular function in obese male population, including the young males with childhood obesity, contributing to increased male infertility, which is a universal trend in the last few decades. Short chain fatty acids (SCFAs) have been recently demonstrated to inhibit progression to metabolic comorbidities. The present study therefore hypothesized that SCFAs, acetate attenuates testicular dysfunction in high fat diet (HFD)-induced obese rat model, possibly by modulating Nrf2/PPAR-γ.

Methods

Adult male Wistar rats weighing 160–190 g were randomly allotted into three groups (n = 6/group): The groups received vehicle (distilled water), 40% HFD and sodium acetate (200 mg/kg) plus 40% HFD respectively. The administration lasted for 12 weeks.

Results

HFD caused obesity, which is characterized with increased body weight and visceral adiposity and insulin resistance/hyperinsulinemia. In addition, it increased testicular lipid deposition, malondialdehyde, pro-inflammatory mediators, lactate/pyruvate ratio, γ-Glutamyl transferase, and circulating leptin as well as decreased testicular glutathione, nitric oxide, Nrf2, PPAR-γ and circulating follicle stimulating hormone and testosterone without a significant change in testicular lactate dehydrogenase, blood glucose and luteinizing hormone when compared to the control group. Nevertheless, administration of acetate reversed the HFD-induced alterations.

Conclusion

The present results demonstrates that HFD causes obesity-driven testicular dysfunction, associated with testicular lipid deposition, oxidative stress, and inflammation. The study in addition suggests the restoration of testicular function in obese animals by acetate, an effect that is accompanied by elevated Nrf2/PPAR-γ.

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Acknowledgements

The authors appreciate the financial support of the management of Afe Babalola University, Ado-Ekiti, Nigeria, and the technical support of Bridge-Biotech, GRA, Ilorin, Nigeria.

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Authors and Affiliations

  1. Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, P.M.B. 5454, Ado-Ekiti, 360101, Nigeria

    Kehinde S. Olaniyi, Christopher O. Akintayo, Adesola A. Oniyide, Adams O. Omoaghe & Mosunmola B. Oyeleke

  2. Neuroscience Unit, Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, 360101, Nigeria

    Kehinde S. Olaniyi & Adedamola A. Fafure

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  1. Kehinde S. Olaniyi
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  2. Christopher O. Akintayo
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Contributions

KSO conceived and designed the research. KSO and COA conducted the experiments. KSO analyzed and interpreted the data. KSO, COA, AAO, AOO, MBO and AAF drafted the manuscript, read, revised and approved the final manuscript.

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Correspondence to Kehinde S. Olaniyi.

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Olaniyi, K.S., Akintayo, C.O., Oniyide, A.A. et al. Acetate supplementation restores testicular function by modulating Nrf2/PPAR-γ in high fat diet-induced obesity in Wistar rats. J Diabetes Metab Disord 20, 1685–1696 (2021). https://doi.org/10.1007/s40200-021-00924-x

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