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Centrally administered urocortin 2 decreases gorging on high-fat diet in both diet-induced obesity-prone and -resistant rats

International Journal of Obesity volume 37, pages 1515–1523 (2013)Cite this article

Subjects

Abstract

Objective:

Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to have a role in obesity risk. The present study tested the hypothesis that (i) the microstructure of chronic high-fat diet intake differs between genetically selected diet-induced obesity (DIO) and diet-resistant (DR) rats, and (ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats.

Design:

Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 μg).

Results:

Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 μg, suppressing high-fat diet intake by ∼40% at the 3 μg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with two-third less water.

Conclusions:

Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically prone DIO rats, which otherwise show a ‘gorging’ meal pattern. These results open new opportunities of investigation toward treating some forms of DIO.

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Acknowledgements

This is manuscript 21959 from The Scripps Research Institute. We recognize the editorial assistance of Michael Arends, the administrative assistance of Mary Gichuhi and the technical assistance of Dahai Jung, Jeanette Helfers, Molly Brennan and Bob Lintz. We thank Jean Rivier (The Salk Institute) for generously providing the peptides. This research was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; DK026741, DK070118, DK076896 (EPZ) and DK30066 (BEL)), the National Institute on Drug Abuse (NIDA; DA023680 and DA030425 (PC)), the National Institute on Alcohol Abuse and Alcoholism (NIAAA; AA016731 (VS)), the National Institute of Mental Health (NIMH; MH091945 (PC) and MH093650 (VS)), the University of Alabama at Birmingham Small Animal Phenotyping Core (P30DK056336 and P60DK079626 (TRN)) and the Research Service of the Veterans Administration.

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  1. P Cottone and V Sabino: These authors contributed equally to this work.

Authors and Affiliations

  1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA

    P Cottone, V Sabino & E P Zorrilla

  2. Departments of Pharmacology and Psychiatry, Laboratory of Addictive Disorders, Boston University School of Medicine, Boston, MA, USA

    P Cottone & V Sabino

  3. Harold L. Dorris Neurological Research Institute, The Scripps Research Institute, La Jolla, CA, USA

    P Cottone, V Sabino & E P Zorrilla

  4. Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA

    T R Nagy

  5. Departments of Psychology, and Departments of Psychiatry and Behavioral Neurosciences, and Nutrition and Food Sciences, College of Liberal Arts and Sciences, and Internal Medicine, School of Medicine, Wayne State University, Detroit, MI, USA

    D V Coscina

  6. Neurology Service (127C), VA Medical Center, East Orange, NJ, USA

    B E Levin

  7. Department of Neurology and Neurosciences, New Jersey Medical School, UMDNJ, Newark, NJ, USA

    B E Levin

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  1. P Cottone
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Correspondence to P Cottone or E P Zorrilla.

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Cottone, P., Sabino, V., Nagy, T. et al. Centrally administered urocortin 2 decreases gorging on high-fat diet in both diet-induced obesity-prone and -resistant rats. Int J Obes 37, 1515–1523 (2013). https://doi.org/10.1038/ijo.2013.22

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