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  • Bariatric and Metabolic Surgery Original Article
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Improvements in hippocampal-dependent memory and microglial infiltration with calorie restriction and gastric bypass surgery, but not with vertical sleeve gastrectomy

International Journal of Obesity volume 38, pages 349–356 (2014)Cite this article

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Abstract

Background:

Much recent evidence suggest that obesity and related comorbidities contribute to cognitive decline, including the development of non age-related dementia and Alzheimer’s disease. Obesity is a serious threat to public health, and few treatments offer proven long-term weight loss. In fact, bariatric surgery remains the most effective long-term therapy to reduce weight and alleviate other aspects of the metabolic syndrome (MetS). Unlike the demonstrated benefits of caloric restriction to prevent weight gain, few if any studies have compared various means of weight loss on central nervous system function and hippocampal-dependent cognitive processes.

Design and Results:

Our studies comprise the first direct comparisons of caloric restriction to two bariatric surgeries (Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG)) on cognitive function. Weight loss following caloric restriction, RYGB and VSG was associated with generalized improvements in metabolic health and hippocampal-dependent learning, as measured in the radial arm maze and spontaneous alternation tests. However, VSG-treated rats exhibited deficits on spatial learning tasks in the Morris water maze. In addition, whereas VSG animals had elevated hippocampal inflammation, comparable to that of obese controls, RYGB and calorie-restricted (pair-fed, PF) controls exhibited an amelioration of inflammation, as measured by the microglial protein ionized calcium binding adaptor molecule 1 (IBA1). We also assessed whether GHR (ghrelin) replacement would attenuate hippocampal inflammation in VSG, as post-surgical GHR levels are significantly reduced in VSG relative to RYGB and PF rats. However, GHR treatment did not attenuate the hippocampal inflammation.

Conclusion:

Although VSG was comparably effective at reducing body weight and improving glucose regulation as RYGB, VSG did not appear to confer an equal benefit on cognitive function and markers of inflammation.

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Acknowledgements

The work of the laboratories is supported in part by NIH Awards DK56863, DK57900, U01CA141464, DK082480, MH069860, DK08248, DK017844, DK067550, HD052112, and also from Ethicon Endo-Surgery Inc., F Hoffman-La Roche Ltd., Pfizer Inc. and Novo Nordisk A/S. BEG is supported by NIH Award 1F32HD68103.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Internal Medicine, Diabetes and Metabolism, The University of Cincinnati College of Medicine, Cincinnati, OH, USA

    B E Grayson, J Tong & R J Seeley

  2. Department of Psychiatry and Behavioral Neuroscience, The University of Cincinnati College of Medicine, Cincinnati, OH, USA

    M F Fitzgerald, A P Hakala-Finch, V M Ferris, D P Begg, S C Woods & S C Benoit

  3. Center for Behavioral Neuroscience, College of Arts and Sciences, American University, Washington, DC, USA

    T L Davidson

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Competing interests

RJS and SCB have received research support from Ethicon Endo-Surgery. In addition, RJS has received support from Mannkind, Novo Nordisk, Ablaris, Pfizer and Roche. RJS has served on scientific advisory boards for Ethicon Endo-Surgery, Angiochem, Novartis and Novo Nordisk; RJS is a paid speaker for Merck, Ethicon Endo-Surgery and Novo Nordisk. The remaining authors declare no conflict of interest.

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Author Contributions

BEG, MFF, APH, VMF, DPB and SCB were responsible for executing and analyzing experiments. BEG, DPB, JT, SCW, TLD and SCB were responsible for planning experiments, interpretation of data, and literature and drafting of the manuscript.

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Grayson, B., Fitzgerald, M., Hakala-Finch, A. et al. Improvements in hippocampal-dependent memory and microglial infiltration with calorie restriction and gastric bypass surgery, but not with vertical sleeve gastrectomy. Int J Obes 38, 349–356 (2014). https://doi.org/10.1038/ijo.2013.100

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  • DOI: https://doi.org/10.1038/ijo.2013.100

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