Insulin sensitivity is preserved in mice made obese by feeding a high starch diet

Abstract

Obesity is generally associated with insulin resistance in liver and muscle and increased risk of developing type 2 diabetes, however there is a population of obese people that remain insulin sensitive. Similarly, recent work suggests that mice fed high carbohydrate diets can become obese without apparent glucose intolerance. To investigate this phenomenon further, we fed mice either a high fat (Hi-F) or high starch (Hi-ST) diet and measured adiposity, glucose tolerance, insulin sensitivity and tissue lipids compared to control mice fed a standard laboratory chow. Both Hi-ST and Hi-F mice accumulated a similar amount of fat and tissue triglyceride compared to chow-fed mice. However while Hi-F diet mice developed glucose intolerance as well as liver and muscle insulin resistance (assessed via euglycemic/hyperinsulinemic clamp), obese Hi-ST mice maintained glucose tolerance and insulin action similar to lean, chow-fed controls. This preservation of insulin action despite obesity in Hi-ST mice was associated with differences in de novo lipogenesis and levels of C22:0 ceramide in liver and C18:0 ceramide in muscle. This indicates that dietary manipulation can influence insulin action independently of the level of adiposity and that the presence of specific ceramide species correlate with these differences.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files; source data files have been provided for Figures 1,2,3,4,5, and 6.

Article and author information

Author details

  1. Amanda E Brandon

    School of Medical Sciences, University of Sydney, Sydney, Australia
    For correspondence
    amanda.brandon@sydney.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4996-7189
  2. Lewin Small

    Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9767-9464
  3. Tuong-Vi Nguyen

    Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Eurwin Suryana

    Diabetes and Metabolism Division, Garvan Institute of Medical Research, Syndey, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Henry Gong

    School of Medical Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Christian Yassmin

    School of Medical Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Sarah E Hancock

    Department of Pharmacology, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Tamara Pulpitel

    School of Life and Environmental Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  9. Sophie Stonehouse

    School of Life and Environmental Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Letisha Prescott

    School of Life and Environmental Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  11. Melkam A Kebede

    School of Life and Environmental Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9686-7378
  12. Belinda Yau

    School of Life and Environmental Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  13. Lake-Ee Quek

    School of Mathematics and Statistics, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  14. Greg M Kowalski

    Institute for Physical Activity and Nutrition, Deakin University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  15. Clinton R Bruce

    Institute for Physical Activity and Nutrition, Deakin University, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0515-3343
  16. Nigel Turner

    Department of Pharmacology, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  17. Gregory J Cooney

    School of Medical Sciences, University of Sydney, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Health and Medical Research Council (Fellowship 1003313)

  • Gregory J Cooney

National Health and Medical Research Council (Program grant 535921)

  • Gregory J Cooney

Diabetes Australia Research Trust (Grant)

  • Gregory J Cooney

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental procedures performed were approved by the Garvan Institute/St Vincent's Hospital Animal Ethics Committee and were in accordance with the National Health and Medical Research Council of Australia's guidelines on animal experimentation (protocol number 14_07).

Copyright

© 2022, Brandon et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Amanda E Brandon
  2. Lewin Small
  3. Tuong-Vi Nguyen
  4. Eurwin Suryana
  5. Henry Gong
  6. Christian Yassmin
  7. Sarah E Hancock
  8. Tamara Pulpitel
  9. Sophie Stonehouse
  10. Letisha Prescott
  11. Melkam A Kebede
  12. Belinda Yau
  13. Lake-Ee Quek
  14. Greg M Kowalski
  15. Clinton R Bruce
  16. Nigel Turner
  17. Gregory J Cooney
(2022)
Insulin sensitivity is preserved in mice made obese by feeding a high starch diet
eLife 11:e79250.
https://doi.org/10.7554/eLife.79250

Share this article

https://doi.org/10.7554/eLife.79250

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