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Animal Models

Eating in mice with gastric bypass surgery causes exaggerated activation of brainstem anorexia circuit

International Journal of Obesity volume 40, pages 921–928 (2016)Cite this article

Subjects

Abstract

Background/Objective:

Obesity and metabolic diseases are at an alarming level globally and increasingly affect children and adolescents. Gastric bypass and other bariatric surgeries have proven remarkably successful and are increasingly performed worldwide. Reduced desire to eat and changes in eating behavior and food choice account for most of the initial weight loss and diabetes remission after surgery, but the underlying mechanisms of altered gut–brain communication are unknown.

Subjects/Methods:

To explore the potential involvement of a powerful brainstem anorexia pathway centered around the lateral parabrachial nucleus (lPBN), we measured meal-induced neuronal activation by means of c-Fos immunohistochemistry in a new high-fat diet-induced obese mouse model of Roux-en-Y gastric bypass (RYGB) at 10 and 40 days after RYGB or sham surgery.

Results:

Voluntary ingestion of a meal 10 days after RYGB, but not after sham surgery, strongly and selectively activates calcitonin gene-related peptide neurons in the external lPBN as well as neurons in the nucleus tractus solitarius, area postrema and medial amygdala. At 40 days after surgery, meal-induced activation in all these areas was greatly diminished and did not reach statistical significance.

Conclusions:

The neural activation pattern and dynamics suggest a role of the brainstem anorexia pathway in the early effects of RYGB on meal size and food intake that may lead to adaptive neural and behavioral changes involved in the control of food intake and body weight at a lower level. However, selective inhibition of this pathway will be required for a more causal implication.

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Acknowledgements

We thank Neelima Gonugunta for help with immunohistochemistry. This study was supported by the National Institutes of Health Grants DK047348 (to H-RB), DK085495 (to JY) and DK092587 (to HM).

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Authors and Affiliations

  1. Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    M B Mumphrey, Z Hao, R L Townsend, L M Patterson, H Münzberg, C D Morrison, J Ye & H-R Berthoud

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  1. M B Mumphrey
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  2. Z Hao
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  3. R L Townsend
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Correspondence to H-R Berthoud.

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Mumphrey, M., Hao, Z., Townsend, R. et al. Eating in mice with gastric bypass surgery causes exaggerated activation of brainstem anorexia circuit. Int J Obes 40, 921–928 (2016). https://doi.org/10.1038/ijo.2016.38

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