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Caloric restriction overcomes pre-diabetes and hypertension induced by a high fat diet and renal artery stenosis

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Abstract

Background

Calorie restriction (CR) is a type of dietary intervention that is essential in weight loss through modulation of critical metabolic control pathways, is well established and understood in cases of systemic arterial hypertension, however, its role in renovascular hypertension is still unclear.

Methods

Rats were divided into three groups: SHAM, and two groups that underwent surgery to clip the left renal artery and induce renovascular hypertension (OH and OHR). The SHAM diet was as follows: 14 weeks normolipidic diet; OH: 2 weeks normolipidic diet + 12 weeks hyperlipidic diet, both ad libitum; OHR, 2 weeks normolipidic diet + 8 weeks ad libitum high-fat diet + 4 weeks 40% calorie-restricted high-fat diet.

Results

Rats in the OHR group had decreased blood pressure, body weight, and glucose levels. Reductions in insulinemia and in lipid and islet fibrotic areas in the OHR group were observed, along with increased insulin sensitivity and normalization of insulin-degrading enzyme levels. The expression of nicotinamide phosphoribosyltransferase (NAMPT), insulin receptor (IR), sirtuin 1 (SIRT1), and complex II proteins were increased in the liver tissue of the OHR group. Strong correlations, whether positive or negative, were evaluated via Spearman’s model between SIRT1, AMPK, NAMPT, PGC-1α, and NNMT expressions with the restoration of normal blood pressure, weight loss, glycemic and lipid panel, and mitochondrial adaptation.

Conclusion

CR provided short-term beneficial effects to recover the physiological parameters induced by a high-fat diet and renal artery stenosis in obese and hypertensive animals. These benefits, even in the short term, can provide physiological benefits in the long term.

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Acknowledgements

The authors are grateful to Edvaldo Costa, BSc, Sr Mateus Eduardo Bortolanza da Silva, Sra Ana Cristina Pires Menegheti, and Renata Barbieri for their excellent technical assistance.

Funding

This work was supported by a grant from the Pesquisa Instuticional Uniararas (PROPesq-FHO).

Author information

Author notes

  1. Michelle Sabino de Souza Nunes Faria and Vinicíus Eduardo Pimentel have contributed equally to this work.

Authors and Affiliations

  1. Graduate Program in Biomedical Sciences, Centro Universitário da Fundação Hermínio Ometto, FHO, Araras, São Paulo, Brazil

    Michelle Sabino de Souza Nunes Faria, Júlia Venturini Helaehil, Bruna Fontana Thomazini, Camila Andréa de Oliveira & Maria Esméria Corezola do Amaral

  2. Programa de Pós-Graduação em Imunologia Básica e Aplicada da Faculdade de Medicina de Ribeirão Preto, Ribeirão Prêto, São Paulo, Brazil

    Vinicíus Eduardo Pimentel

  3. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Vinicíus Eduardo Pimentel & Pedro Vieira da Silva-Neto

  4. Biomedical College, Centro Universitário da Fundação Hermínio Ometto, FHO, Araras, São Paulo, Brazil

    Vinicíus Eduardo Pimentel, Júlia Venturini Helaehil, Mayara Correa Bertolo & Nathalia Tonus Horas Santos

  5. Programa de Pós-graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas - UFAM, Manaus, Amazonas, Brazil

    Pedro Vieira da Silva-Neto

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  1. Michelle Sabino de Souza Nunes Faria
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Correspondence to Maria Esméria Corezola do Amaral.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Manuscript submitted to a pre-print platform Research Square, the https://doi.org/10.21203/rs.3.rs1085770/v1 and this work is licensed under a CC BY 4.0 License and pre-print plataform bioRxiv 2021.03.30.437684; https://doi.org/10.1101/2021.03.30.437684.

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11033_2022_7370_MOESM1_ESM.docx

Supplementary file1 (DOCX 282 kb). Figure 1: (A) Hepatic Glycogen and (B) Muscle Glycogen. Data expressed for SHAM, OH, and OHR groups. The bars represent the mean ± SEM, p<0.05 indicates a significant difference based on one-way ANOVA, Tukey post hoc test. Figure 2: Protein expression in the liver tissues of animals of the SHAM, OH, and OHR groups: (A) pAkt/Akt, (B) PGC1α, (C) FOXO, (D) SIRT3 and (E) NNMT. The bars represent the mean ± SEM, p<0.05 indicates a significant difference based on one-way ANOVA, Tukey post hoc test.

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de Souza Nunes Faria, M.S., Pimentel, V.E., Helaehil, J.V. et al. Caloric restriction overcomes pre-diabetes and hypertension induced by a high fat diet and renal artery stenosis. Mol Biol Rep 49, 5883–5895 (2022). https://doi.org/10.1007/s11033-022-07370-9

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