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Maternal Roux-en-Y gastric bypass impairs insulin action and endocrine pancreatic function in male F1 offspring

  • Carla Bruna Pietrobon
  • Iala Milene Bertasso
  • Rosane Aparecida Ribeiro
  • Ana Claudia Paiva Alegre-Maller
  • Camila Lubaczeuski
  • Antonio Carlos Boschero
  • Allan Cezar Faria Araújo
  • Sandra Lucinei Balbo
  • Maria Lúcia BonfleurEmail author
Original Contribution

Abstract

Purpose

Obesity is predominant in women of reproductive age. Roux-en-Y gastric bypass (RYGB) is the most common bariatric procedure that is performed in obese women for weight loss and metabolic improvement. However, some studies suggest that this procedure negatively affects offspring. Herein, using Western diet (WD)-obese female rats, we investigated the effects of maternal RYGB on postnatal body development, glucose tolerance, insulin secretion and action in their adult male F1 offspring.

Methods

Female Wistar rats consumed a Western diet (WD) for 18 weeks, before being submitted to RYGB (WD-RYGB) or SHAM (WD-SHAM) operations. After 5 weeks, WD-RYGB and WD-SHAM females were mated with control male breeders, and the F1 offspring were identified as: WD-RYGB-F1 and WD-SHAM-F1.

Results

The male F1 offspring of WD-RYGB dams exhibited decreased BW, but enhanced total nasoanal length gain. At 120 days of age, WD-RYGB-F1 rats displayed normal fasting glycemia and glucose tolerance but demonstrated reduced insulinemia and higher glucose disappearance after insulin stimulus. In addition, these rodents presented insulin resistance in the gastrocnemius muscle and retroperitoneal fat, as judged by lower Akt phosphorylation after insulin administration, but an increase in this protein in the liver. Finally, the islets from WD-RYGB-F1 rats secreted less insulin in response to glucose and displayed increased β-cell area and mass.

Conclusions

RYGB in WD dams negatively affected their F1 offspring, leading to catch-up growth, insulin resistance in skeletal muscle and white fat, and β-cell dysfunction. Therefore, our data are the first to demonstrate that the RYGB in female rats may aggravate the metabolic imprinting induced by maternal WD consumption, in their male F1 descendants. However, since we only used male F1 rats, further studies are necessary to demonstrate if such effect may also occur in female F1 offspring from dams that underwent RYGB operation.

Keywords

Bariatric operation Insulin resistance Insulin secretion Maternal programming Metabolic imprinting Obesity 

Notes

Acknowledgements

We are grateful to Assis Roberto Escher for animal care and the graduate student Gabriela Alves Bronczek for all their help with experiments.

Funding

This study forms part of the MSc thesis of C. B. Pietrobon and was supported by Grants from Fundação Araucária (155/2013), Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq, Processo no. 447190/2014-8), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, PROAP, no.: 817693/2015) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2015/12611-0).

Compliance with ethical standards

Conflict of interest

All authors who contributed to the study state that there was no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Carla Bruna Pietrobon
    • 1
  • Iala Milene Bertasso
    • 1
  • Rosane Aparecida Ribeiro
    • 2
  • Ana Claudia Paiva Alegre-Maller
    • 1
  • Camila Lubaczeuski
    • 3
  • Antonio Carlos Boschero
    • 3
  • Allan Cezar Faria Araújo
    • 4
  • Sandra Lucinei Balbo
    • 1
  • Maria Lúcia Bonfleur
    • 1
    Email author
  1. 1.Laboratório de Fisiologia Endócrina e Metabolismo (LAFEM), Centro de Ciências Biológicas e da SaúdeUniversidade Estadual do Oeste do Paraná (UNIOESTE)CascavelBrazil
  2. 2.Universidade Federal do Rio de Janeiro (UFRJ)MacaéBrazil
  3. 3.Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de BiologiaUniversidade Estadual de Campinas (UNICAMP)CampinasBrazil
  4. 4.Centro de Ciências Médicas e Farmacêuticas, UNIOESTECascavelBrazil

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