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Animal Models

Changes in morphology and function of adrenal cortex in mice fed a high-fat diet

International Journal of Obesity volume 39, pages 321–330 (2015)Cite this article

Subjects

Abstract

Background/objectives:

Obesity is a major risk factor for the development of type 2 diabetes and other debilitating diseases. Obesity and diabetes are intimately linked with altered levels of adrenal steroids. Elevated levels of these hormones induce insulin resistance and cause cardiovascular diseases. The mechanisms underlying obesity-related alterations in adrenal steroids are still not well understood. Here, we investigated how diet-induced obesity affects the morphology and function of the mouse adrenal cortex.

Methods:

We fed animals either a high-fat diet (HFD) or a normal diet (60% kcal from fat or 10% kcal from fat, respectively) for 18 weeks. We then assessed various aspects of adrenal gland morphology and function, as well as basal plasma concentrations of steroid hormones and ACTH.

Results:

We show that adrenal glands of mice fed a HFD release more corticosterone and aldosterone, resulting in higher plasma levels. This increase is driven by adrenal cortical hyperplasia, and by increased expression of multiple genes involved in steroidogenesis. We demonstrate that diet-induced obesity elevates Sonic hedgehog signaling in Gli1-positive progenitors, which populate the adrenal capsule and give rise to the steroidogenic cells of the adrenal cortex. Feeding animals with a HFD depletes Gli1-positive progenitors, as the adrenal cortex expands.

Conclusions:

This work provides insight into how diet-induced obesity changes the biology of the adrenal gland. The association of these changes with increased Shh signaling suggests possible therapeutic strategies for obesity-related steroid hormone dysfunction.

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Acknowledgements

We gratefully acknowledge Celso Gomez-Sanchez, Ken Morohashi and Peter King for providing antibodies. We are grateful to Marc Bickle from the Technology Development Studio (MPI-CBG), for designing and implementing pipelines for the image analysis. We thank Julia Jarrels and Britta Schilling from the DNA Microarray Facility (MPI-CBG) for their assistance in real-time quantitative PCR analyses. We acknowledge Biomedical Services (MPI-CBG) for their help in animal husbandry and handling. We are grateful to Susann Malik for technical assistance. This work was supported by DFG grant, KFO 252.

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Author notes

  1. M M Swierczynska

    Present address: 4Current address: Biozentrum, University of Basel, Basel, Switzerland.,

  2. V Lamounier-Zepter and S Eaton: These authors contributed equally to this work.

Authors and Affiliations

  1. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

    M M Swierczynska, I Mateska & S Eaton

  2. Department of Internal Medicine III, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany

    M M Swierczynska, I Mateska, S R Bornstein, T Chavakis & V Lamounier-Zepter

  3. Department of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany

    M Peitzsch & G Eisenhofer

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Correspondence to S Eaton.

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Swierczynska, M., Mateska, I., Peitzsch, M. et al. Changes in morphology and function of adrenal cortex in mice fed a high-fat diet. Int J Obes 39, 321–330 (2015). https://doi.org/10.1038/ijo.2014.102

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