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Bariatric Surgery

Brain effect of bariatric surgery in people with obesity

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Abstract

Background/Objectives

The link between obesity and brain function is a fascinating but still an enigmatic topic. We evaluated the effect of Roux-en-Y gastric bypass (RYGB) on peripheral glucose metabolism, insulin sensitivity, brain glucose utilization and cognitive abilities in people with obesity.

Subjects/Methods

Thirteen subjects with obesity (F/M 11/2; age 44.4 ± 9.8 years; BMI 46.1 ± 4.9 kg/m2) underwent 75-g OGTT during a [18F]FDG dynamic brain PET/CT study at baseline and 6 months after RYGB. At the same timepoints, cognitive performance was tested with Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Trail making test (TMT) and Token test (TT). Glucose, insulin, C-peptide, GLP-1, GIP, and VIP levels were measured during OGTT. Leptin and BDNF levels were measured before glucose ingestion.

Results

RYGB resulted in significant weight loss (from 46.1 ± 4.9 to 35.3 ± 5.0 kg/m2; p < 0.01 vs baseline). Insulin sensitivity improved (disposition index: from 1.1 ± 0.2 to 2.9 ± 1.1; p = 0.02) and cerebral glucose metabolic rate (CMRg) declined in various brain areas (all p ≤ 0.01). MMSE and MoCA score significantly improved (p = 0.001 and p = 0.002, respectively). TMT and TT scores showed a slight improvement. A positive correlation was found between CMRg change and HOMA-IR change in the caudate nucleus (ρ = 0.65, p = 0.01). Fasting leptin decreased (from 80.4 ± 13.0 to 16.1 ± 2.4 ng/dl; p = 0.001) and correlated with CMRg change in the hippocampus (ρ = 0.50; p = 0.008). CMRg change was correlated with cognitive scores changes on the TMT and TT (all p = 0.04 or less).

Conclusions

Bariatric surgery improves CMRg directly related to a better cognitive testing result. This study highlights the potential pleiotropic effects of bariatric surgery.

Trial registry number

NCT03414333.

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Fig. 1: Cerebral metabolic rate of glucose in a patient before (upper panel) and after (lower panel) Roux-en-Y Gastric Bypass.
Fig. 2: Glucose metabolic rate in brain regions before (white bars) and after (dark bars) Roux-en-Y Gastric Bypass.

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Data availability

Data are available on request from AD and GD.

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Acknowledgements

We thank Dr. L. Giusti for the support in performing lab tests.

Funding

This research was conducted with support from the University of Pisa (Project Code: PRA_2016_44) and from the Italian Ministry of the University (Project code 2017L8Z2EM).

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, Section of Diabetes and Metabolic Diseases, University of Pisa, Nuovo Ospedale Santa Chiara, Pisa, Italy

    Angela Dardano, Annamaria Ciccarone, Veronica Sancho Bornez, Stefano Del Prato & Giuseppe Daniele

  2. Regional Center of Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine, University of Pisa, Nuovo Ospedale Santa Chiara, Pisa, Italy

    Gayane Aghakhanyan & Duccio Volterrani

  3. Section Bariatric Surgery Unit, Nuovo Ospedale Santa Chiara, Pisa, Italy

    Carlo Moretto & Rosario Bellini

  4. Obesity and Lipodystrophy Center, Endocrinology Unit, University of Pisa, Nuovo Ospedale Santa Chiara, Pisa, Italy

    Giovanni Ceccarini & Ferruccio Santini

Authors
  1. Angela Dardano
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  2. Gayane Aghakhanyan
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  3. Carlo Moretto
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  4. Annamaria Ciccarone
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  5. Rosario Bellini
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  6. Veronica Sancho Bornez
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  7. Giovanni Ceccarini
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  9. Duccio Volterrani
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  10. Stefano Del Prato
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  11. Giuseppe Daniele
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Contributions

AD, GD, and SDP contributed to the conception and design of the experiments and were responsible for data collection, analysis, and interpretation; AD, GD, AC, GC, and FS recruited the subjects; GD and AD performed clinical examinations; AD also performed neurocognitive examinations; VSB performed lab measurements; CM and RB performed surgery; GA and DV performed PET studies and analysis; GD performed statistical analysis; AD wrote the first version of the paper; AD, SDP, and GD discussed the results and wrote the final version of the paper. All authors approved the final version of the manuscript for submission. AD and GD are guarantors of this work, who have full access to all the data in this study and take responsibility for the integrity and accuracy of the data.

Corresponding author

Correspondence to Stefano Del Prato.

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Dardano, A., Aghakhanyan, G., Moretto, C. et al. Brain effect of bariatric surgery in people with obesity. Int J Obes 46, 1671–1677 (2022). https://doi.org/10.1038/s41366-022-01162-8

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