Feeding mice a high fat, low carbohydrate (Hi-F) diet results in obesity and glucose intolerance. Switching from a Hi-F back to a chow has been shown to reverse the diet-induced glucose intolerance within a week. However, this improvement was associated with a decrease in food intake, body fat content and tissue lipid levels . This makes it difficult to conclude whether a change of diet or loss of fat leads to improved glucose homeostasis. We have shown that feeding a high-starch (Hi-ST) diet to mice produced obesity while maintaining glucose tolerance similar to lean chow-fed mice. We have used this model to investigate whether switching diet composition between the Hi-F to Hi-ST can alter glucose tolerance without changing body composition.
Mice were fed either chow, Hi-F or Hi-ST diet for 12 weeks. After this initial feeding period, mice in the Hi-F group were switched from Hi-ST and Hi-ST switched Hi-F for 7 days. Body composition, food intake and glucose tolerance were assessed before and after switch.
Fat mass was similarly increased in the Hi-F and Hi-ST mice compared to chow and this did not change after the 7-day switch. Energy intake was higher in the dietary groups and remained increased post-switch. Prior to the switch, Hi-F mice were glucose intolerant, while H-ST were similar to controls. After only 7 days, the Hi-ST->Hi-F became glucose intolerant, while the Hi-F->Hi-ST had glucose tolerance similar to chow controls. This improvement was not associated with changes in liver triglyceride levels, but with changes in mRNA and protein levels of enzymes in liver involved in de novo lipogenesis.
Collectively these findings suggest that variations in glucose homeostasis in mice are largely independent of whole-body adiposity level and more closely associated with the ratio of macronutrients in a diet.