The effect of acute dietary changes on glucose metabolism in obese mice

Jinfeng Lin, Tamara Pulpitel, Gregory Cooney and Amanda Brandon

School of Medical Sciences, Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia

Feeding mice a high fat, low carbohydrate (Hi-F) diet results in obesity and glucose intolerance. Acutely changing a Hi-F diet to a chow diet has been shown to normalise diet-induced glucose intolerance within a week. However, the metabolic improvements were associated with reduced energy intake, total fat mass, and reduced tissue lipid levels. This makes it difficult to conclude whether the improved glucose tolerance was the result of fat loss or the change of diet. 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 changes in body composition.
Male C57BL6 mice were fed either a 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 1-week 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 1 week, the Hi-ST Hi-F mice 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.


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