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Duodenal-Jejunal Bypass Restores Insulin Action and Βeta-Cell Function in Hypothalamic-Obese Rats

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Abstract

Background

Bariatric operations are frequently used to improve metabolic profile and comorbidities in obese subjects, but the effects of this procedure in hypothalamic-obese (HyO) patients are controversial. Here, using HyO rats, we investigate the effects of duodenal-jejunal bypass (DJB) upon obesity, serum lipid levels, glucose tolerance, and insulin action and secretion.

Methods

Hypothalamic obesity was induced in male rats by the administration of monosodium glutamate [4 g/kg body weight (BW), HyO group] during the first 5 days of life. Control (CTL) group received saline (1.25 g/kg BW). At 90 days of age, HyO rats were submitted to DJB (HyO DJB group) or sham surgery. After 2 months, lipid levels, glucose tolerance, obesity parameters, and insulin sensitivity and secretion were verified.

Results

HyO rats displayed obesity, hypertriglyceridemia, hypercholesterolemia, glucose intolerance, and hyperinsulinemia. A higher HOMA-IR and no alteration in the ratio of phospho (p)-Akt related to Akt protein content in the liver, after insulin stimulus, demonstrated that HyO rats were insulin resistant. Islets isolated from HyO rats hypersecreted insulin in response to glucose and carbachol (Cch). At 2 months after DJB, HyO rats still displayed higher fat stores, but showed normal serum lipids and insulin levels. The HyO DJB group displayed better glucose tolerance, associated with a normal hepatic insulin activation of Akt. Normal glucose and Cch-induced insulin secretion was observed in HyO DJB islets.

Conclusions

DJB ameliorated glucose homeostasis, restored hepatic insulin action, and normalized islet function in HyO rats, indicating that this surgery may be useful for the treatment of hypothalamic obesity.

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Acknowledgments

We are grateful to Assis Roberto Escher for animal care and Nicola Conran for editing English.

Funding

This study was supported by grants from Fundação Araucária, Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Conflicts of Interest

All contributing authors declare that they have no conflicts of interest.

Statement of Informed Consent

This article does not contain any studies with human participants.

Statement of Human and Animal Rights

All experiments were approved by the University’s Committee on Ethics in Animal Experimentation (CEEAAP/UNIOESTE, protocol no. 62/10), and all applicable institutional and/or national guidelines for the care and use of animals were followed.

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Authors and Affiliations

  1. Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil, CEP: 858119-110

    Maria Lúcia Bonfleur, Audrei Pavanello, Raul Soster, Camila Lubaczeuski & Sandra Lucinei Balbo

  2. Universidade Federal do Rio de Janeiro, Campus UFRJ-Macaé, Macaé, RJ, Brazil

    Rosane Aparecida Ribeiro

  3. Centro de Ciências Médicas e Farmacêuticas, UNIOESTE, Cascavel, PR, Brazil

    Allan Cezar Faria Araujo

  4. Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil

    Antonio Carlos Boschero

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  1. Maria Lúcia Bonfleur
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  2. Rosane Aparecida Ribeiro
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Correspondence to Maria Lúcia Bonfleur.

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Bonfleur, M.L., Ribeiro, R.A., Pavanello, A. et al. Duodenal-Jejunal Bypass Restores Insulin Action and Βeta-Cell Function in Hypothalamic-Obese Rats. OBES SURG 25, 656–665 (2015). https://doi.org/10.1007/s11695-014-1427-3

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