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Gender differences in the renal changes induced by a prolonged high-fat diet in rats with altered renal development

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Abstract

The mechanisms involved in renal dysfunction induced by high-fat diet (HFD) in subjects with altered renal development (ARDev) are understudied. The objective of this study is to examine whether there are sex-dependent differences in the mechanisms involved in the hypertension and deterioration of renal function in SD rats with prolonged HFD and ARDev. The role of angiotensin II (Ang II) in the arterial pressure (AP) increments, the renal hemodynamic sensitivity to Ang II, glomerular damage and changes in fat abdominal volume, plasma adipokine levels, renal NADPHp67phox expression, and renal infiltration of immune cells were examined. Hypertension and deterioration of renal function were enhanced (P < 0.05) in both sexes of rats with HFD and ARDev. The decrease (P < 0.05) of AP elicited by candesartan in hypertensive rats was similar to that induced by the simultaneous administration of candesartan and apocynin. The greater (P < 0.05) renal vasoconstriction induced by Ang II in both sexes of rats with HFD and ARDev was accompanied by an enhanced (P < 0.05) infiltration of CD-3 cells and macrophages in the renal cortex and renal medulla. The increments (P < 0.05) in the renal expression of NADPHp67phox and glomeruloesclerosis were greater (P < 0.05) in males than in females with HFD and ARDev. Our results suggest that the hypertension and deterioration of renal function induced by HFD in rats with ARDev are Ang II-dependent and mediated by increments in oxidative stress and immune system activation. Sex-dependent increments in oxidative stress and glomerular damage may contribute to the deterioration of renal function in these rats.

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Availability of data and material

All raw data that support the findings of this study will be available without restriction from the corresponding author on reasonable request.

Funding

This work was supported by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (PI16/01556) (co-funded by European Regional Development Fund/European Social Fund “A way to make Europe/Investing in your future) and Fondos FEDER.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, University of Murcia, 30100, Murcia, Spain

    Juan M. Moreno, Virginia Reverte, F. Javier Salazar & María T. Llinás

  2. Biomedical Research Institute in Murcia, Murcia, Spain

    Juan M. Moreno, Carlos M. Martinez, Virginia Reverte, F. Javier Salazar & María T. Llinás

  3. Department of Pathology, School of Veterinary, University of Murcia, Murcia, Spain

    Carlos de Jodar & Antonio Bernabé

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  1. Juan M. Moreno
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Contributions

- Moreno JM, Salazar FJ, and Llinas MT contributed to the conception and design of the work.

- All authors contributed to the acquisition, analysis, or interpretation of data and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to F. Javier Salazar.

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Ethics approval

The procuration of animals, the husbandry, and the experiments conform to the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes. Approval was obtained from the ethics committee of the University of Murcia, Spain.

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All authors revised the manuscript and approved the version to be published.

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The authors declare no competing interests.

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F. Javier Salazar and María T. Llinás share senior authorship.

Key Points

• An early and prolonged high-fat diet induces a greater increment of arterial pressure in male than in female rats with a reduced nephron endowment.

• Renal damage is enhanced by a high-fat diet in both sexes of rats with altered renal development.

• Angiotensin II is involved in the hypertension and deterioration of renal function in rats with a prolonged high-fat diet and reduced nephron endowment.

• The activation of oxidative stress and inflammatory pathways is greater in male than in female rats with a prolonged high-fat diet and reduced nephron endowment.

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Moreno, J.M., Martinez, C.M., de Jodar, C. et al. Gender differences in the renal changes induced by a prolonged high-fat diet in rats with altered renal development. J Physiol Biochem 77, 431–441 (2021). https://doi.org/10.1007/s13105-021-00815-y

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  • DOI: https://doi.org/10.1007/s13105-021-00815-y

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