Insulin sensitivity is preserved in mice made obese by feeding a high starch diet
- University of Sydney, Australia
- Garvan Institute of Medical Research, Australia
- University of New South Wales, Australia
- Deakin University, Australia
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
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.
Reviewing Editor
- Jonathan S Bogan, Yale School of Medicine, United States
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).
Version history
- Received: April 5, 2022
- Preprint posted: May 26, 2022 (view preprint)
- Accepted: November 16, 2022
- Accepted Manuscript published: November 17, 2022 (version 1)
- Version of Record published: November 30, 2022 (version 2)
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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Insulin sensitivity is preserved in mice made obese by feeding a high starch diet
eLife 11:e79250.
https://doi.org/10.7554/eLife.79250
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