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Caloric restriction prevents inflammation and insulin dysfunction in middle-aged ovariectomized mice

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Abstract

Background

Loss of ovarian function is associated with increased visceral fat. In this study, we aimed to study the effects of caloric restriction (CR) on metabolism in ovariectomized mice.

Methods and results

Female, 8–12-month-old mice were divided into three groups: OVX (ovariectomized mice), OVXR (40% CR) and Sham. CR increased insulin sensitivity and glucose tolerance. AMPK phosphorylation was observed in the liver of OVXR mice. CR also increased hepatic cholesterol and triglyceride levels. The reductions in the level of TBARS in the serum and liver and of H2O2 in the liver of OVXR mice suggested alterations in the redox state of the liver. Although expression of catalase protein was reduced by CR, expression of superoxide dismutase was not altered by CR. Although interleukin IL-6 and IL-10 levels in OVXR mice were similar to those in Sham mice, macrophage infiltration was reduced in OVXR mice. OVXR mice had increased sirtuin1 levels and decreased sirtuin3 levels in the liver.

Conclusions

In conclusion, CR improved the condition of ovariectomized mice by reducing adiposity and increasing insulin sensitivity and glucose tolerance through a mechanism that may involve AMPK.

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Data Availability

Data generated or analyzed during this study are available form the corresponding author upon reasonable request.

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Acknowledgements

We thank Ana Cristina Pires Menegheti, Bruno Alves Cia, Lucas Orzari, Mateus Eduardo Bortolanza da Silva, and Renata Barbieri for technical assistance.

Funding

This work was supported by the Herminio Ometto Foundation.

Author information

Author notes

  1. Leticia Sapatini and Bruno Calsa are both co-first authors.

Authors and Affiliations

  1. Graduate Program in Biomedical Sciences, University Center of Hermínio Ometto Foundation, Av. Maximiliano Barutto nº 500, Jardim Universitário, Araras, SP, 13607-339, Brazil

    Leticia Roberta Leme Sapatini, Bruno Calsa, Júlia Venturini Helaehil, Gabriela Bortolança Chiarotto & Maria Esméria Corezola do Amaral

  2. Fetal Programming and Hydroelectrolyte Metabolism laboratory, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, UNICAMP, São Paulo, Brazil

    Bruno Calsa

  3. Physiotherapy College, University Center of Hermínio Ometto Foundation, FHO, Araras, SP, Brazil

    Lais Jorge Marim

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  1. Leticia Roberta Leme Sapatini
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  2. Bruno Calsa
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  3. Lais Jorge Marim
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Contributions

Sapatini LRL: Data curation, Investigation, Visualization, Writing – original draft. Calsa B: Data curation, Formal analysis, Investigation, Validation, Visualization, Writing – original draft, review and editing. Marim LJ: Investigation. Helaehil JV: Data curation, Investigation. Amaral MEC: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Project administration, Resources, Supervision, Validation, Visualization, Writing – review & editing.

Corresponding author

Correspondence to Maria Esméria Corezola do Amaral.

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Competing interests

No conflicts of interest, financial or otherwise, are declared by the authors.

Ethics approval

The project was approved by the Committee on Ethics in Animal Use (CEUA) under protocol #009/2020 of University Center of Hermínio Ometto Foundation, Araras, SP, Brazil.

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bioRxiv preprint https://doi.org/10.1101/2023.02.09.527836.

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Sapatini, L.R.L., Calsa, B., Marim, L.J. et al. Caloric restriction prevents inflammation and insulin dysfunction in middle-aged ovariectomized mice. Mol Biol Rep 50, 5675–5685 (2023). https://doi.org/10.1007/s11033-023-08508-z

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