School of Medical Sciences, University of Sydney, Sydney, Australia; Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, Australia
School of Life and Environmental Sciences, Charles Perkins Centre, University of Sydney, Sydney, Australia
Belinda Yau
School of Life and Environmental Sciences, Charles Perkins Centre, University of Sydney, Sydney, Australia
Lake-Ee Quek
School of Mathematics and Statistics, Charles Perkins Centre, University of Sydney, Sydney, Australia
Greg M Kowalski
Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Australia; Metabolic Research Unit, School of Medicine, Deakin University, Melbourne, Australia
Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Melbourne, Australia
Nigel Turner
Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia
Gregory J Cooney
School of Medical Sciences, University of Sydney, Sydney, Australia; Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, Australia
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 euglycaemic/hyperinsulinaemic 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 correlates with these differences.
