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Animal Models

Role of aquaporin-7 in ghrelin- and GLP-1-induced improvement of pancreatic β-cell function after sleeve gastrectomy in obese rats

International Journal of Obesity volume 41, pages 1394–1402 (2017)Cite this article

Subjects

Abstract

Background/Objectives:

Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues as well as for pancreatic insulin secretion. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in β-cells, and AQP12, an aquaporin related to pancreatic damage, in the improvement of pancreatic function and steatosis after sleeve gastrectomy in diet-induced obese rats.

Subjects/Methods:

Male Wistar obese rats (n=125) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by sleeve-gastrectomized animals) interventions. The tissue distribution and expression of AQPs in the rat pancreas were analyzed by real-time PCR, western blotting and immunohistochemistry. The effect of ghrelin isoforms and glucagon-like peptide 1 (GLP-1) on insulin secretion, triacylglycerol (TG) accumulation and AQP expression was determined in vitro in RIN-m5F β-cells.

Results:

Sleeve gastrectomy reduced pancreatic β-cell apoptosis, steatosis and insulin secretion. Lower ghrelin and higher GLP-1 concentrations were also found after bariatric surgery. Acylated and desacyl ghrelin increased TG content, whereas GLP-1 increased insulin release in RIN-m5F β-cells. Sleeve gastrectomy was associated with an upregulation of AQP7 together with a normalization of the increased AQP12 levels in the rat pancreas. Interestingly, ghrelin and GLP-1 repressed AQP7 and AQP12 expression in RIN-m5F β-cells. AQP7 protein was negatively correlated with intracellular lipid accumulation in acylated ghrelin-treated cells and with insulin release in GLP-1-stimulated β-cells.

Conclusions:

AQP7 upregulation in β-cells after sleeve gastrectomy contributes, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol used for insulin release triggered by GLP-1 rather than for ghrelin-induced TG biosynthesis.

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Acknowledgements

We thank Beatriz Ramírez (Metabolic Research Laboratory, Clínica Universidad de Navarra) for technical assistance as well as all the staff of the breeding house of the University of Navarra. This work was supported by Fondo de Investigación Sanitaria-FEDER (FIS PI12/00515, PI13/01430, PI16/00221 and PI16/01217) from the Spanish Instituto de Salud Carlos III as well as by the Department of Health of Gobierno de Navarra (61/2014). CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III, Spain.

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Authors and Affiliations

  1. Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain

    L Méndez-Giménez, S Becerril, V Catalán, J Gómez-Ambrosi, G Frühbeck & A Rodríguez

  2. CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain

    L Méndez-Giménez, S Becerril, R Moncada, V Valentí, V Catalán, J Gómez-Ambrosi, G Frühbeck & A Rodríguez

  3. Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisboa, Portugal

    S P Camões, I V da Silva, C Rodrigues, J P Miranda & G Soveral

  4. Department of Anesthesia, Clínica Universidad de Navarra, Pamplona, Spain

    R Moncada

  5. Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain

    V Valentí

  6. Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain

    G Frühbeck

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  1. L Méndez-Giménez
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Correspondence to G Frühbeck or A Rodríguez.

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Méndez-Giménez, L., Becerril, S., Camões, S. et al. Role of aquaporin-7 in ghrelin- and GLP-1-induced improvement of pancreatic β-cell function after sleeve gastrectomy in obese rats. Int J Obes 41, 1394–1402 (2017). https://doi.org/10.1038/ijo.2017.135

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