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Maternal low-protein diet during lactation combined with early overfeeding impair male offspring’s long-term glucose homeostasis

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Abstract

Purpose

The early-life nutritional environment affects long-term glucose homeostasis, we investigated the effects of maternal low-protein diet combined with postnatal early overfeeding on the male offspring’s glucose homeostasis in adulthood.

Methods

Only male rats were used, and their delivery was considered postnatal-day 0 (PN0). Wistar rats’ dams were divided into control (NP) or low-protein diet (LP). LP dams remained on the diet until PN14, after which all animals were supplied with the control diet. At PN2, litters were adjusted to 9 (control-NL) or 3 (postnatal-overfeeding-PO) pups, resulting in four experimental groups: NP-NL, NP-PO, LP-NL, and LP-PO. Litters were weaned on PN21. At PN80, a batch of animals from all experimental groups underwent surgery for cannula implantation, followed by intravenous glucose tolerance test (ivGTT), but the insulinogenic index (ISI) was calculated. At PN81, animals were euthanized and tissues were collected.

Results

LP-diet and early postnatal-overfeeding were effective in promoting the expected biometric outcomes at PN21 and PN81, but the LP-PO animals present a biometric profile similar to the control (NP-NL) group. Postnatal-overfeeding increased fasting glycemia in LP-PO animals (p < 0.01). In the ivGTT, postnatal-overfeeding elevated the glycemia (p < 0.0001), exacerbated in LP-PO animals (p < 0.0001). Insulinemia was reduced by both, maternal LP-diet and postnatal-overfeeding, with a higher degree of reduction in LP-PO animals (p < 0.0001). Maternal LP-diet and postnatal-overfeeding reduced the ISI (p < 0.0001). Factors interaction lead the LP-PO to a lower ISI compared to all other groups (p < 0.0001).

Conclusions

The combination of low-protein diet in breastfeeding dams with postnatal overfeeding disturbed the offspring’s glucose metabolism in adulthood.

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Funding

The present study was financially supported by the Brazilian Federal Research Agencies: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

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Author notes

  1. These authors contributed equally: Douglas Lopes Almeida, Fernando Salgueiro Simões.

Authors and Affiliations

  1. Laboratory of Secretion Cell Biology, Department of Biotechnology, Cell Biology and Genetics, State University of Maringá, Maringá, PR, Brazil

    Douglas Lopes Almeida, Fernando Salgueiro Simões, Lucas Paulo Jacinto Saavedra, Ana Maria Praxedes Moraes, Camila Cristina Ianoni Matiusso, Ananda Malta, Kesia Palma-Rigo & Paulo Cesar de Freitas Mathias

  2. Plenavita Clinics, 1021 rua Julio Prestes, Ribeirão Preto, SP, Brazil

    Fernando Salgueiro Simões

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  1. Douglas Lopes Almeida
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Correspondence to Douglas Lopes Almeida.

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The authors declare that they have no conflict of interest.

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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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Almeida, D.L., Simões, F.S., Saavedra, L.P.J. et al. Maternal low-protein diet during lactation combined with early overfeeding impair male offspring’s long-term glucose homeostasis. Endocrine 63, 62–69 (2019). https://doi.org/10.1007/s12020-018-1719-9

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  • DOI: https://doi.org/10.1007/s12020-018-1719-9

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