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Animal Models

Altered circadian feeding behavior and improvement of metabolic syndrome in obese Tac1-deficient mice

International Journal of Obesity volume 41, pages 1798–1804 (2017)Cite this article

Subjects

Abstract

Background:

Metabolic function is regulated by the interplay of central and peripheral factors that ultimately regulate food intake (FI) and energy expenditure. The tachykinin substance P (SP) has been identified as a novel regulator of energy balance, however, the mechanisms underlying this effect are ill-defined and conflicting data regarding the role of SP on FI have been reported by different groups.

Objective:

To further characterize the metabolic role of the Tac1 gene products (SP and neurokinin A) in mice through a series of genetic, metabolic and behavioral studies in Tac1-deficient mice.

Results:

Tac1−/− mice are leaner than controls and display reduced FI and altered feeding circadian rhythm, supported by disrupted expression of the clock genes Cry1/2, Per1/2 in the suprachiasmatic nucleus, mediobasal hypothalamus (MBH) and liver, as well as increased proopiomelanocortin expression in the MBH. Tac1 ablation induced resistance to obesity, improved glucose tolerance, prevented insulin resistance under high-fat diet, increased activation of brown adipose tissue and improved hepatic steatosis. Moreover, deletion of Tac1 in ob/ob mice ameliorated body weight gain in females only but was sufficient to decrease fat and triglyceride content in the liver of males.

Conclusions:

These results provide further evidence that Tac1 controls circadian feeding behavior and metabolism in mice through mechanisms that involve the regulation of the melanocortin system. In addition, these studies suggest that the blockade of SP may offer a new method to treat metabolic syndrome.

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Acknowledgements

We thank Dr Alex Banks and Katherine Leclair for their help with the Comprehensive Lab Animal Monitoring System studies. This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development through cooperative agreement U54 HD028138, R01 HD019938 and R01 HD082314 to UBK; R00 HD071970, Charles H. Hood Foundation for Child Health Research Program to VMN.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Diabetes and Hypertension, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    C A Maguire, S León, R S Carroll, U B Kaiser & V M Navarro

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  1. C A Maguire
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  2. S León
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  3. R S Carroll
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  4. U B Kaiser
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Correspondence to V M Navarro.

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Maguire, C., León, S., Carroll, R. et al. Altered circadian feeding behavior and improvement of metabolic syndrome in obese Tac1-deficient mice. Int J Obes 41, 1798–1804 (2017). https://doi.org/10.1038/ijo.2017.185

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