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Animal Models

Metabolic effects of bariatric surgery in mouse models of circadian disruption

International Journal of Obesity volume 39, pages 1310–1318 (2015)Cite this article

Subjects

Abstract

Background/Objectives:

Mounting evidence supports a link between circadian disruption and metabolic disease. Humans with circadian disruption (for example, night-shift workers) have an increased risk of obesity and cardiometabolic diseases compared with the non-disrupted population. However, it is unclear whether the obesity and obesity-related disorders associated with circadian disruption respond to therapeutic treatments as well as individuals with other types of obesity.

Subjects/Methods:

Here, we test the effectiveness of the commonly used bariatric surgical procedure, Vertical Sleeve Gastrectomy (VSG), in mouse models of genetic and environmental circadian disruption.

Results:

VSG led to a reduction in body weight and fat mass in both ClockΔ19 mutant and constant-light mouse models (P<0.05), resulting in an overall metabolic improvement independent of circadian disruption. Interestingly, the decrease in body weight occurred without altering diurnal feeding or activity patterns (P>0.05). Within circadian-disrupted models, VSG also led to improved glucose tolerance and lipid handling (P<0.05).

Conclusions:

Together these data demonstrate that VSG is an effective treatment for the obesity associated with circadian disruption, and that the potent effects of bariatric surgery are orthogonal to circadian biology. However, as the effects of bariatric surgery are independent of circadian disruption, VSG cannot be considered a cure for circadian disruption. These data have important implications for circadian-disrupted obese patients. Moreover, these results reveal new information about the metabolic pathways governing the effects of bariatric surgery as well as of circadian disruption.

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Acknowledgements

Grant Support: This work was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (F32 DK097867-01, D.Arble; DK082480-01, D.Sandoval; and R01 DK093848-01, R.Seeley).

Author Contributions

DMA designed and performed experiments, analyzed data and wrote the manuscript. DAS, FWT, SCW and RJS contributed to experimental design and edited the manuscript.

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Authors and Affiliations

  1. Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    D M Arble, D A Sandoval & R J Seeley

  2. Neurobiology and Neurology, Northwestern University, Evanston, IL, USA

    F W Turek

  3. Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA

    S C Woods

Authors
  1. D M Arble
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  2. D A Sandoval
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  3. F W Turek
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  4. S C Woods
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  5. R J Seeley
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Corresponding author

Correspondence to R J Seeley.

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Competing interests

DMA, FWT and SCW have no conflicts to declare. DAS receives funding from Ethicon Endo-Surgery, Novo Nordisk and Boehringer Ingelheim International. RJS receives funding from Ethicon Endo-Surgery, Ablaris Therapeutics, Inc., Novo Nordisk, Novartis, Angiochem, Eisai, Forest Pharmaceuticals, Givaudan, Zealand Pharmaceuticals and Boehringer Ingelheim International.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Arble, D., Sandoval, D., Turek, F. et al. Metabolic effects of bariatric surgery in mouse models of circadian disruption. Int J Obes 39, 1310–1318 (2015). https://doi.org/10.1038/ijo.2015.54

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